O60939 · SCN2B_HUMAN
- ProteinSodium channel regulatory subunit beta-2
- GeneSCN2B
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids215 (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 (PubMed:19808477, PubMed:23559163, PubMed:26894959, PubMed:30765605, PubMed:30765606, PubMed:35277491, PubMed:36823201).
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:19808477, PubMed:23559163, PubMed:26894959).
The accessory beta subunits participate in localization and functional modulation of the Nav channels (PubMed:19808477, PubMed:23559163).
Modulates the activity of SCN1A/Nav1.1, SCN2A/Nav1.2, SCN2A/Nav1.3, SCN5A/Nav1.5, SCN8A/Nav1.6, SCN9A/Nav1.7 and SCN10A/Nav1.8 (PubMed:19808477, PubMed:23559163, PubMed:26894959, PubMed:30765605, PubMed:30765606, PubMed:35277491, PubMed:36823201).
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:19808477, PubMed:23559163, PubMed:26894959).
The accessory beta subunits participate in localization and functional modulation of the Nav channels (PubMed:19808477, PubMed:23559163).
Modulates the activity of SCN1A/Nav1.1, SCN2A/Nav1.2, SCN2A/Nav1.3, SCN5A/Nav1.5, SCN8A/Nav1.6, SCN9A/Nav1.7 and SCN10A/Nav1.8 (PubMed:19808477, PubMed:23559163, PubMed:26894959, PubMed:30765605, PubMed:30765606, PubMed:35277491, PubMed:36823201).
Features
Showing features for site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Site | 56 | Binds SCN2A | ||||
Sequence: Y | ||||||
Site | 135 | Binds SCN2A | ||||
Sequence: R |
GO annotations
Keywords
- Biological process
- Ligand
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameSodium channel regulatory subunit beta-2
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionO60939
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Cell membrane ; Single-pass type I membrane protein
Note: Clusters at the axon initial segment and node of Ranvier, the specialized neuronal subcellular domains involved in action potentials generation and propagation.
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 30-157 | Extracellular | ||||
Sequence: MEVTVPATLNVLNGSDARLPCTFNSCYTVNHKQFSLNWTYQECNNCSEEMFLQFRMKIINLKLERFQDRVEFSGNPSKYDVSVMLRNVQPEDEGIYNCYIMNPPDRHRGHGKIHLQVLMEEPPERDST | ||||||
Transmembrane | 158-179 | Helical | ||||
Sequence: VAVIVGASVGGFLAVVILVLMV | ||||||
Topological domain | 180-215 | Cytoplasmic | ||||
Sequence: VKCVRRKKEQKLSTDDLKTEEEGKTDGEGNPDDGAK |
Keywords
- Cellular component
Disease & Variants
Involvement in disease
Atrial fibrillation, familial, 14 (ATFB14)
- 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:615378
Natural variants in ATFB14
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_070229 | 28 | R>Q | in ATFB14; the mutant results in reduced sodium currents and altered channel gating when coexpressed with SCN5A in a heterologous expression system; dbSNP:rs72544145 | |
VAR_029131 | 28 | R>W | in ATFB14; the mutant results in reduced sodium currents and altered channel gating when coexpressed with SCN5A in a heterologous expression system; dbSNP:rs17121819 |
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_070229 | 28 | in ATFB14; the mutant results in reduced sodium currents and altered channel gating when coexpressed with SCN5A in a heterologous expression system; dbSNP:rs72544145 | |||
Sequence: R → Q | ||||||
Natural variant | VAR_029131 | 28 | in ATFB14; the mutant results in reduced sodium currents and altered channel gating when coexpressed with SCN5A in a heterologous expression system; dbSNP:rs17121819 | |||
Sequence: R → W | ||||||
Natural variant | VAR_029132 | 47 | in dbSNP:rs17121818 | |||
Sequence: R → H | ||||||
Mutagenesis | 55 | Does not bind alpha subunit. Loss of ability to protect alpha subunit from inhibition by the spider protoxin-II. | ||||
Sequence: C → A or S | ||||||
Natural variant | VAR_070230 | 211 | found in a patient with Brugada syndrome; uncertain significance; induces a reduction in sodium current density most likely by decreasing SCN5A protein cell surface expression; dbSNP:rs587777023 | |||
Sequence: D → G |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 294 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, glycosylation, disulfide bond, modified residue, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Signal | 1-29 | UniProt | |||||
Sequence: MHRDAWLPRPAFSLTGLSLFFSLVPPGRS | |||||||
Chain | PRO_0000014931 | 30-215 | UniProt | Sodium channel regulatory subunit beta-2 | |||
Sequence: MEVTVPATLNVLNGSDARLPCTFNSCYTVNHKQFSLNWTYQECNNCSEEMFLQFRMKIINLKLERFQDRVEFSGNPSKYDVSVMLRNVQPEDEGIYNCYIMNPPDRHRGHGKIHLQVLMEEPPERDSTVAVIVGASVGGFLAVVILVLMVVKCVRRKKEQKLSTDDLKTEEEGKTDGEGNPDDGAK | |||||||
Glycosylation | 42 | UniProt | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | |||||||
Disulfide bond | 50↔127 | UniProt | |||||
Sequence: CTFNSCYTVNHKQFSLNWTYQECNNCSEEMFLQFRMKIINLKLERFQDRVEFSGNPSKYDVSVMLRNVQPEDEGIYNC | |||||||
Disulfide bond | 55 | UniProt | Interchain; with alpha subunit | ||||
Sequence: C | |||||||
Glycosylation | 66 | UniProt | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | |||||||
Disulfide bond | 72↔75 | UniProt | |||||
Sequence: CNNC | |||||||
Glycosylation | 74 | UniProt | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | |||||||
Modified residue | 192 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 192 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 204 | UniProt | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 204 | PRIDE | Phosphothreonine | ||||
Sequence: T |
Keywords
- PTM
Proteomic databases
PTM databases
Expression
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:22992729).
The beta subunit SCN2B is disulfide-linked to the pore-forming alpha subunit (PubMed:22992729).
Interacts with SCN1A; regulatory subunit of SCN1A/Nav1.1 (PubMed:22992729).
Interacts with SCN2A; regulatory subunit of SCN2A/Nav1.2 (PubMed:26894959, PubMed:30765605).
Interacts with SCN3A; regulatory subunit of SCN3A/Nav1.3 (PubMed:35277491).
Interacts with SCN5A; regulatory subunit of SCN5A/Nav1.5 (PubMed:19808477).
Interacts with SCN8A; regulatory subunit of SCN8A/Nav1.6 (PubMed:36823201).
Interacts with SCN9A; regulatory subunit of SCN9A/Nav1.7 (PubMed:30765606).
Interacts with SCN10A; regulatory subunit of SCN10A/Nav1.8 (By similarity).
Interacts with TNR; may play a crucial role in clustering and regulation of activity of SCN2B-containing Nav channels at nodes of Ranvier (By similarity).
The beta subunit SCN2B is disulfide-linked to the pore-forming alpha subunit (PubMed:22992729).
Interacts with SCN1A; regulatory subunit of SCN1A/Nav1.1 (PubMed:22992729).
Interacts with SCN2A; regulatory subunit of SCN2A/Nav1.2 (PubMed:26894959, PubMed:30765605).
Interacts with SCN3A; regulatory subunit of SCN3A/Nav1.3 (PubMed:35277491).
Interacts with SCN5A; regulatory subunit of SCN5A/Nav1.5 (PubMed:19808477).
Interacts with SCN8A; regulatory subunit of SCN8A/Nav1.6 (PubMed:36823201).
Interacts with SCN9A; regulatory subunit of SCN9A/Nav1.7 (PubMed:30765606).
Interacts with SCN10A; regulatory subunit of SCN10A/Nav1.8 (By similarity).
Interacts with TNR; may play a crucial role in clustering and regulation of activity of SCN2B-containing Nav channels at nodes of Ranvier (By similarity).
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain, region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 32-154 | Ig-like C2-type | ||||
Sequence: VTVPATLNVLNGSDARLPCTFNSCYTVNHKQFSLNWTYQECNNCSEEMFLQFRMKIINLKLERFQDRVEFSGNPSKYDVSVMLRNVQPEDEGIYNCYIMNPPDRHRGHGKIHLQVLMEEPPER | ||||||
Region | 187-215 | Disordered | ||||
Sequence: KEQKLSTDDLKTEEEGKTDGEGNPDDGAK |
Sequence similarities
Belongs to the sodium channel auxiliary subunit SCN2B (TC 8.A.17) family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
- Length215
- Mass (Da)24,326
- Last updated1998-08-01 v1
- Checksum94A30A60A32683F3
Computationally mapped potential isoform sequences
There is 1 potential isoform mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A590UJS3 | A0A590UJS3_HUMAN | SCN2B | 92 |
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 2 | in Ref. 1; AAC26013 | ||||
Sequence: H → Q | ||||||
Sequence conflict | 8 | in Ref. 1; AAC26013 | ||||
Sequence: P → L | ||||||
Sequence conflict | 15 | in Ref. 1; AAC26013 | ||||
Sequence: T → N | ||||||
Sequence conflict | 48 | in Ref. 1; AAC26013 | ||||
Sequence: L → Q | ||||||
Sequence conflict | 68 | in Ref. 1; AAC26013 | ||||
Sequence: T → S | ||||||
Sequence conflict | 156 | in Ref. 3; AAD47196 | ||||
Sequence: S → F | ||||||
Sequence conflict | 178-179 | in Ref. 1; AAC26013 | ||||
Sequence: MV → TA |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF007783 EMBL· GenBank· DDBJ | AAC26013.1 EMBL· GenBank· DDBJ | mRNA | ||
AF049498 EMBL· GenBank· DDBJ | AAC05274.1 EMBL· GenBank· DDBJ | mRNA | ||
AF049497 EMBL· GenBank· DDBJ | AAC05208.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF049496 EMBL· GenBank· DDBJ | AAC05208.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF107028 EMBL· GenBank· DDBJ | AAD47196.1 EMBL· GenBank· DDBJ | mRNA | ||
U87555 EMBL· GenBank· DDBJ | AAF21472.1 EMBL· GenBank· DDBJ | mRNA | ||
AY358945 EMBL· GenBank· DDBJ | AAQ89304.1 EMBL· GenBank· DDBJ | mRNA | ||
BC036793 EMBL· GenBank· DDBJ | AAH36793.1 EMBL· GenBank· DDBJ | mRNA |