Q07699 · SCN1B_HUMAN
- ProteinSodium channel regulatory subunit beta-1
- GeneSCN1B
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids218 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Regulatory subunit of multiple voltage-gated sodium (Nav) channels directly mediating the depolarization of 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:14622265, PubMed:15525788, PubMed:18464934, PubMed:19710327, PubMed:29992740, PubMed:36696443, PubMed:8125980, PubMed:8394762).
The accessory beta subunits participate in localization and functional modulation of the Nav channels (PubMed:15525788, PubMed:19710327, PubMed:29992740).
Modulates the activity of SCN1A/Nav1.1, SCN2A/Nav1.2, SCN3A/Nav1.3, SCN4A/Nav1.4, SCN5A/Nav1.5, SCN8A/Nav1.6, SCN9A/Nav1.7 and SCN10A/Nav1.8 (PubMed:14622265, PubMed:15525788, PubMed:18464934, PubMed:30765606, PubMed:36696443, PubMed:8125980, PubMed:8394762).
The accessory beta subunits participate in localization and functional modulation of the Nav channels (PubMed:15525788, PubMed:19710327, PubMed:29992740).
Modulates the activity of SCN1A/Nav1.1, SCN2A/Nav1.2, SCN3A/Nav1.3, SCN4A/Nav1.4, SCN5A/Nav1.5, SCN8A/Nav1.6, SCN9A/Nav1.7 and SCN10A/Nav1.8 (PubMed:14622265, PubMed:15525788, PubMed:18464934, PubMed:30765606, PubMed:36696443, PubMed:8125980, PubMed:8394762).
Isoform 2
Cell adhesion molecule that plays a critical role in neuronal migration and pathfinding during brain development. Stimulates neurite outgrowth (PubMed:21994374).
Has no regulatory function on the SCN2A sodium channel complex (PubMed:14622265).
Has no regulatory function on the SCN2A sodium channel complex (PubMed:14622265).
GO annotations
Keywords
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameSodium channel regulatory subunit beta-1
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ07699
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Isoform 1
Cell membrane ; Single-pass type I membrane protein
Note: Detected at nodes of Ranvier on the sciatic nerve.
Isoform 2
Note: Detected on Purkinje cells and their cell projections and on neuronal cell projections.
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 19-157 | Extracellular | ||||
Sequence: GGCVEVDSETEAVYGMTFKILCISCKRRSETNAETFTEWTFRQKGTEEFVKILRYENEVLQLEEDERFEGRVVWNGSRGTKDLQDLSIFITNVTYNHSGDYECHVYRLLFFENYEHNTSVVKKIHIEVVDKANRDMASI | ||||||
Transmembrane | 158-179 | Helical | ||||
Sequence: VSEIMMYVLIVVLTIWLVAEMI | ||||||
Topological domain | 180-218 | Cytoplasmic | ||||
Sequence: YCYKKIAAATETAAQENASEYLAITSESKENCTGVQVAE |
Keywords
- Cellular component
Disease & Variants
Involvement in disease
Generalized epilepsy with febrile seizures plus 1 (GEFSP1)
- Note
- DescriptionA rare autosomal dominant, familial condition with incomplete penetrance and large intrafamilial variability. Patients display febrile seizures persisting sometimes beyond the age of 6 years and/or a variety of afebrile seizure types. This disease combines febrile seizures, generalized seizures often precipitated by fever at age 6 years or more, and partial seizures, with a variable degree of severity.
- See alsoMIM:604233
Natural variants in GEFSP1
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_010165 | 121 | C>W | in GEFSP1; can rescue the loss of function and defective trafficking to cell membrane phenotype of the SCN1A variant Thr-1852; dbSNP:rs104894718 | |
VAR_067341 | 125 | R>L | in GEFSP1; dbSNP:rs759839781 |
Brugada syndrome 5 (BRGDA5)
- Note
- DescriptionA tachyarrhythmia characterized by right bundle branch block and ST segment elevation on an electrocardiogram (ECG). It can cause the ventricles to beat so fast that the blood is prevented from circulating efficiently in the body. When this situation occurs, the individual will faint and may die in a few minutes if the heart is not reset.
- See alsoMIM:612838
Atrial fibrillation, familial, 13 (ATFB13)
- Note
- DescriptionA familial form of atrial fibrillation, a common sustained cardiac rhythm disturbance. Atrial fibrillation is characterized by disorganized atrial electrical activity and ineffective atrial contraction promoting blood stasis in the atria and reduces ventricular filling. It can result in palpitations, syncope, thromboembolic stroke, and congestive heart failure.
- See alsoMIM:615377
Natural variants in ATFB13
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_070219 | 85 | R>H | in ATFB13; the mutant results in highly reduced sodium currents and altered channel gating when coexpressed with SCN5A in a heterologous expression system; dbSNP:rs16969925 | |
VAR_070220 | 153 | D>N | in ATFB13; the mutant results in reduced sodium currents when coexpressed with SCN5A in a heterologous expression system; dbSNP:rs72550247 |
Developmental and epileptic encephalopathy 52 (DEE52)
- Note
- DescriptionA form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE52 inheritance is autosomal recessive.
- See alsoMIM:617350
Natural variants in DEE52
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_078019 | 106 | I>T | in DEE52; uncertain significance | |
VAR_078020 | 125 | R>C | in DEE52; severely decreased channel localization at the cell membrane; dbSNP:rs1135401736 |
Features
Showing features for natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_062523 | 25 | found in a patient with idiopathic childhood epilepsy; likely pathogenic; de novo mutation; loss of function in increasing sodium channel activity; dbSNP:rs786205837 | |||
Sequence: D → N | ||||||
Natural variant | VAR_070219 | 85 | in ATFB13; the mutant results in highly reduced sodium currents and altered channel gating when coexpressed with SCN5A in a heterologous expression system; dbSNP:rs16969925 | |||
Sequence: R → H | ||||||
Natural variant | VAR_062524 | 87 | found in a patient with non-specific cardiac conduction defects; likely pathogenic; dbSNP:rs121434627 | |||
Sequence: E → Q | ||||||
Natural variant | VAR_078019 | 106 | in DEE52; uncertain significance | |||
Sequence: I → T | ||||||
Natural variant | VAR_010165 | 121 | in GEFSP1; can rescue the loss of function and defective trafficking to cell membrane phenotype of the SCN1A variant Thr-1852; dbSNP:rs104894718 | |||
Sequence: C → W | ||||||
Natural variant | VAR_078020 | 125 | in DEE52; severely decreased channel localization at the cell membrane; dbSNP:rs1135401736 | |||
Sequence: R → C | ||||||
Natural variant | VAR_067341 | 125 | in GEFSP1; dbSNP:rs759839781 | |||
Sequence: R → L | ||||||
Natural variant | VAR_062525 | 138 | in dbSNP:rs72558029 | |||
Sequence: V → I | ||||||
Natural variant | VAR_070220 | 153 | in ATFB13; the mutant results in reduced sodium currents when coexpressed with SCN5A in a heterologous expression system; dbSNP:rs72550247 | |||
Sequence: D → N | ||||||
Natural variant | VAR_062526 | 208 | in dbSNP:rs780958012 | |||
Sequence: K → I | ||||||
Natural variant | VAR_062527 | 211 | in dbSNP:rs150721582 | |||
Sequence: C → Y | ||||||
Natural variant | VAR_062528 | 213 | in dbSNP:rs201209882 | |||
Sequence: G → D |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 343 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for signal, chain, disulfide bond, glycosylation.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Signal | 1-18 | |||||
Sequence: MGRLLALVVGAALVSSAC | ||||||
Chain | PRO_0000014926 | 19-218 | Sodium channel regulatory subunit beta-1 | |||
Sequence: GGCVEVDSETEAVYGMTFKILCISCKRRSETNAETFTEWTFRQKGTEEFVKILRYENEVLQLEEDERFEGRVVWNGSRGTKDLQDLSIFITNVTYNHSGDYECHVYRLLFFENYEHNTSVVKKIHIEVVDKANRDMASIVSEIMMYVLIVVLTIWLVAEMIYCYKKIAAATETAAQENASEYLAITSESKENCTGVQVAE | ||||||
Disulfide bond | 21↔43 | |||||
Sequence: CVEVDSETEAVYGMTFKILCISC | ||||||
Disulfide bond | 40↔121 | |||||
Sequence: CISCKRRSETNAETFTEWTFRQKGTEEFVKILRYENEVLQLEEDERFEGRVVWNGSRGTKDLQDLSIFITNVTYNHSGDYEC | ||||||
Glycosylation | 93 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 110 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 114 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 135 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N |
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
The overall expression of isoform 1 and isoform 2 is very similar. Isoform 1 is abundantly expressed in skeletal muscle, heart and brain. Isoform 2 is highly expressed in brain and skeletal muscle and present at a very low level in heart, placenta, lung, liver, kidney and pancreas. In brain, isoform 2 is most abundant in the cerebellum, followed by the cerebral cortex and occipital lobe, while isoform 1 levels are higher in the cortex compared to the cerebellum. Isoform 2 is expressed in many regions of the brain, including cerebellar Purkinje cells, cortex pyramidal neurons and many of the neuronal fibers throughout the brain (at protein level). Also detected in dorsal root ganglion, in fibers of the spinal nerve and in cortical neurons and their processes (at protein level).
Gene expression databases
Organism-specific databases
Interaction
Subunit
Voltage-gated sodium (Nav) channel consists of an ion-conducting pore-forming alpha subunit functional on its own that is regulated by one or more beta subunits (PubMed:15525788, PubMed:21994374, PubMed:30190309, PubMed:36696443, PubMed:36823201).
Interacts with SCN1A; regulatory subunit of SCN1A/Nav1.1 (PubMed:15525788, PubMed:17928445, PubMed:21994374).
Interacts with SCN3A; regulatory subunit of SCN3A/Nav1.3 (PubMed:21994374).
Interacts with SCN4A; regulatory subunit of SCN4A/Nav1.4 (PubMed:30190309).
Interacts with SCN5A; regulatory subunit of SCN5A/Nav1.5 (PubMed:21994374).
Interacts with SCN8A; regulatory subunit of SCN8A/Nav1.6 (PubMed:26900580, PubMed:36696443, PubMed:36823201).
Interacts with SCN9A; regulatory subunit of SCN9A/Nav1.7 (PubMed:21994374).Interacts with SCN10A; regulatory subunit of SCN10A/Nav1.8 (By similarity).
Interacts with NFASC (By similarity).
Interacts with TMEM65 (By similarity).
Interacts with SCN1A; regulatory subunit of SCN1A/Nav1.1 (PubMed:15525788, PubMed:17928445, PubMed:21994374).
Interacts with SCN3A; regulatory subunit of SCN3A/Nav1.3 (PubMed:21994374).
Interacts with SCN4A; regulatory subunit of SCN4A/Nav1.4 (PubMed:30190309).
Interacts with SCN5A; regulatory subunit of SCN5A/Nav1.5 (PubMed:21994374).
Interacts with SCN8A; regulatory subunit of SCN8A/Nav1.6 (PubMed:26900580, PubMed:36696443, PubMed:36823201).
Interacts with SCN9A; regulatory subunit of SCN9A/Nav1.7 (PubMed:21994374).Interacts with SCN10A; regulatory subunit of SCN10A/Nav1.8 (By similarity).
Interacts with NFASC (By similarity).
Interacts with TMEM65 (By similarity).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q07699-1 | SCN4A P35499 | 2 | EBI-20974499, EBI-16813249 |
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 22-150 | Ig-like C2-type | ||||
Sequence: VEVDSETEAVYGMTFKILCISCKRRSETNAETFTEWTFRQKGTEEFVKILRYENEVLQLEEDERFEGRVVWNGSRGTKDLQDLSIFITNVTYNHSGDYECHVYRLLFFENYEHNTSVVKKIHIEVVDKA |
Sequence similarities
Belongs to the sodium channel auxiliary subunit SCN1B (TC 8.A.17) family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
This entry describes 2 isoforms produced by Alternative splicing.
Q07699-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- SynonymsBeta-1
- Length218
- Mass (Da)24,707
- Last updated1996-10-01 v1
- Checksum09B812FA3F9E9018
Q07699-2
- Name2
- SynonymsBeta-1B, beta1A, beta1B
- NoteDue to intron 3 retention.
- Differences from canonical
- 150-218: ANRDMASIVSEIMMYVLIVVLTIWLVAEMIYCYKKIAAATETAAQENASEYLAITSESKENCTGVQVAE → GESGAACPFTVTHRRARWRDRWQAVDRTGWLCAWPANRPQQRAEGEGSSPSCPLQLWPLFLSSPRRGQSMPVPHRRSGYRTQLCHLCCMTSGRCLLSLSQRVVLGLPGIIIRCVSRGVV
Computationally mapped potential isoform sequences
There are 5 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A6Q8PGS1 | A0A6Q8PGS1_HUMAN | SCN1B | 227 | ||
A0A6Q8PHF7 | A0A6Q8PHF7_HUMAN | SCN1B | 166 | ||
B4DI92 | B4DI92_HUMAN | SCN1B | 147 | ||
A0A1W2PR05 | A0A1W2PR05_HUMAN | SCN1B | 185 | ||
A0A1W2PS68 | A0A1W2PS68_HUMAN | SCN1B | 235 |
Features
Showing features for alternative sequence.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_041982 | 150-218 | in isoform 2 | |||
Sequence: ANRDMASIVSEIMMYVLIVVLTIWLVAEMIYCYKKIAAATETAAQENASEYLAITSESKENCTGVQVAE → GESGAACPFTVTHRRARWRDRWQAVDRTGWLCAWPANRPQQRAEGEGSSPSCPLQLWPLFLSSPRRGQSMPVPHRRSGYRTQLCHLCCMTSGRCLLSLSQRVVLGLPGIIIRCVSRGVV |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
L10338 EMBL· GenBank· DDBJ | AAA60391.1 EMBL· GenBank· DDBJ | mRNA | ||
L16242 EMBL· GenBank· DDBJ | AAA61277.1 EMBL· GenBank· DDBJ | mRNA | ||
U12193 EMBL· GenBank· DDBJ | AAB97608.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
U12189 EMBL· GenBank· DDBJ | AAB97608.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
U12190 EMBL· GenBank· DDBJ | AAB97608.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
U12191 EMBL· GenBank· DDBJ | AAB97608.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
U12192 EMBL· GenBank· DDBJ | AAB97608.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AY391842 EMBL· GenBank· DDBJ | AAR25552.1 EMBL· GenBank· DDBJ | mRNA | ||
AK313279 EMBL· GenBank· DDBJ | BAG36087.1 EMBL· GenBank· DDBJ | mRNA | ||
DQ677665 EMBL· GenBank· DDBJ | ABQ01236.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BT019923 EMBL· GenBank· DDBJ | AAV38726.1 EMBL· GenBank· DDBJ | mRNA | ||
AC020907 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BC067122 EMBL· GenBank· DDBJ | AAH67122.1 EMBL· GenBank· DDBJ | mRNA |