UniProtKB - Q8IWT1 (SCN4B_HUMAN)
Sodium channel subunit beta-4
SCN4B
Functioni
Modulates channel gating kinetics. Causes negative shifts in the voltage dependence of activation of certain alpha sodium channels, but does not affect the voltage dependence of inactivation. Modulates the susceptibility of the sodium channel to inhibition by toxic peptides from spider, scorpion, wasp and sea anemone venom.
1 PublicationGO - Molecular functioni
- sodium channel regulator activity Source: UniProtKB
- transmembrane transporter binding Source: BHF-UCL
- voltage-gated ion channel activity Source: UniProtKB-KW
- voltage-gated sodium channel activity Source: UniProtKB
- voltage-gated sodium channel activity involved in cardiac muscle cell action potential Source: BHF-UCL
GO - Biological processi
- AV node cell action potential Source: BHF-UCL
- cardiac muscle cell action potential involved in contraction Source: BHF-UCL
- cardiac muscle contraction Source: BHF-UCL
- membrane depolarization during cardiac muscle cell action potential Source: BHF-UCL
- positive regulation of sodium ion transport Source: BHF-UCL
- regulation of heart rate by cardiac conduction Source: BHF-UCL
- regulation of sodium ion transmembrane transporter activity Source: UniProtKB
- regulation of ventricular cardiac muscle cell membrane repolarization Source: BHF-UCL
- sodium ion transmembrane transport Source: BHF-UCL
- sodium ion transport Source: UniProtKB
Keywordsi
Molecular function | Ion channel, Sodium channel, Voltage-gated channel |
Biological process | Ion transport, Sodium transport, Transport |
Ligand | Sodium |
Enzyme and pathway databases
PathwayCommonsi | Q8IWT1 |
Reactomei | R-HSA-445095, Interaction between L1 and Ankyrins R-HSA-5576892, Phase 0 - rapid depolarisation R-HSA-9717207, Sensory perception of sweet, bitter, and umami (glutamate) taste |
SignaLinki | Q8IWT1 |
Protein family/group databases
TCDBi | 8.A.17.2.2, the na(+) channel auxiliary subunit Beta1-Beta4 (sca-Beta) family |
Names & Taxonomyi
Protein namesi | Recommended name: Sodium channel subunit beta-4 |
Gene namesi | Name:SCN4B |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:10592, SCN4B |
MIMi | 608256, gene |
neXtProti | NX_Q8IWT1 |
VEuPathDBi | HostDB:ENSG00000177098 |
Subcellular locationi
Plasma membrane
- Cell membrane 1 Publication; Single-pass type I membrane protein 1 Publication
Plasma Membrane
- intrinsic component of plasma membrane Source: UniProtKB
- plasma membrane Source: GO_Central
- voltage-gated sodium channel complex Source: UniProtKB
Other locations
- intercalated disc Source: BHF-UCL
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 31 – 162 | ExtracellularSequence analysisAdd BLAST | 132 | |
Transmembranei | 163 – 183 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 184 – 228 | CytoplasmicSequence analysisAdd BLAST | 45 |
Keywords - Cellular componenti
Cell membrane, MembranePathology & Biotechi
Involvement in diseasei
Long QT syndrome 10 (LQT10)1 Publication
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_043488 | 179 | L → F in LQT10; increase in late sodium current. 1 PublicationCorresponds to variant dbSNP:rs121434386EnsemblClinVar. | 1 |
Atrial fibrillation, familial, 17 (ATFB17)1 Publication
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_071317 | 162 | V → G in ATFB17. 1 PublicationCorresponds to variant dbSNP:rs587777559EnsemblClinVar. | 1 | |
Natural variantiVAR_071318 | 166 | I → L in ATFB17. 1 PublicationCorresponds to variant dbSNP:rs587777560EnsemblClinVar. | 1 |
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 58 | C → A: Abolishes regulation of channel activity. 1 Publication | 1 | |
Mutagenesisi | 131 | C → A or W: Decreases protein stability. Causes conformation changes that impair interaction with the alpha subunit. 1 Publication | 1 |
Keywords - Diseasei
Atrial fibrillation, Disease variant, Long QT syndromeOrganism-specific databases
DisGeNETi | 6330 |
GeneReviewsi | SCN4B |
MalaCardsi | SCN4B |
MIMi | 611819, phenotype |
OpenTargetsi | ENSG00000177098 |
Orphaneti | 334, Familial atrial fibrillation 101016, Romano-Ward syndrome |
PharmGKBi | PA35007 |
Miscellaneous databases
Pharosi | Q8IWT1, Tbio |
Chemistry databases
DrugBanki | DB05541, Brivaracetam DB00907, Cocaine DB13269, Dichlorobenzyl alcohol DB13961, Fish oil DB00776, Oxcarbazepine DB00243, Ranolazine DB00313, Valproic acid DB00909, Zonisamide |
DrugCentrali | Q8IWT1 |
Genetic variation databases
BioMutai | SCN4B |
DMDMi | 57012701 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 30 | Sequence analysisAdd BLAST | 30 | |
ChainiPRO_0000014937 | 31 – 228 | Sodium channel subunit beta-4Add BLAST | 198 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Glycosylationi | 45 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 53 ↔ 131 | PROSITE-ProRule annotation1 Publication | ||
Disulfide bondi | 58 | Interchain; with alpha subunitPROSITE-ProRule annotation1 Publication | ||
Glycosylationi | 71 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 113 | N-linked (GlcNAc...) asparagineSequence analysis | 1 |
Post-translational modificationi
Keywords - PTMi
Disulfide bond, GlycoproteinProteomic databases
jPOSTi | Q8IWT1 |
MassIVEi | Q8IWT1 |
PaxDbi | Q8IWT1 |
PeptideAtlasi | Q8IWT1 |
PRIDEi | Q8IWT1 |
ProteomicsDBi | 22813 70889 [Q8IWT1-1] 70890 [Q8IWT1-2] |
PTM databases
GlyGeni | Q8IWT1, 3 sites |
iPTMneti | Q8IWT1 |
PhosphoSitePlusi | Q8IWT1 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSG00000177098, Expressed in caudate nucleus and 192 other tissues |
ExpressionAtlasi | Q8IWT1, baseline and differential |
Genevisiblei | Q8IWT1, HS |
Organism-specific databases
HPAi | ENSG00000177098, Tissue enhanced (brain, tongue) |
Interactioni
Subunit structurei
The voltage-sensitive sodium channel consists of an ion conducting pore forming alpha-subunit (SCN2A) regulated by one or more beta subunits (SCN1B, SCN2B, SCN3B and SCN4B). SCN1B and SCN3B are non-covalently associated with SCN2A. SCN2B and SCN4B are disulfide-linked to SCN2A (PubMed:24297919).
1 PublicationBinary interactionsi
Q8IWT1
With | #Exp. | IntAct |
---|---|---|
YIF1A [O95070] | 3 | EBI-23705473,EBI-2799703 |
GO - Molecular functioni
- transmembrane transporter binding Source: BHF-UCL
Protein-protein interaction databases
BioGRIDi | 112235, 5 interactors |
IntActi | Q8IWT1, 1 interactor |
STRINGi | 9606.ENSP00000322460 |
Miscellaneous databases
RNActi | Q8IWT1, protein |
Structurei
Secondary structure
3D structure databases
AlphaFoldDBi | Q8IWT1 |
SMRi | Q8IWT1 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 31 – 148 | Ig-like C2-typeAdd BLAST | 118 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 200 – 228 | DisorderedSequence analysisAdd BLAST | 29 |
Sequence similaritiesi
Keywords - Domaini
Immunoglobulin domain, Signal, Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | ENOG502QTZ6, Eukaryota |
GeneTreei | ENSGT01030000234556 |
HOGENOMi | CLU_104235_0_0_1 |
InParanoidi | Q8IWT1 |
OMAi | EGQYICF |
PhylomeDBi | Q8IWT1 |
TreeFami | TF331728 |
Family and domain databases
Gene3Di | 2.60.40.10, 1 hit |
InterProi | View protein in InterPro IPR007110, Ig-like_dom IPR036179, Ig-like_dom_sf IPR013783, Ig-like_fold IPR003599, Ig_sub IPR013106, Ig_V-set IPR000920, Myelin_P0-rel IPR044572, Na_channel_b4 |
PANTHERi | PTHR13869, PTHR13869, 1 hit PTHR13869:SF14, PTHR13869:SF14, 1 hit |
Pfami | View protein in Pfam PF07686, V-set, 1 hit |
SMARTi | View protein in SMART SM00409, IG, 1 hit |
SUPFAMi | SSF48726, SSF48726, 1 hit |
PROSITEi | View protein in PROSITE PS50835, IG_LIKE, 1 hit |
s (3)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 3 produced by isoformsialternative splicing. AlignAdd to basketThis isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MPGAGDGGKA PARWLGTGLL GLFLLPVTLS LEVSVGKATD IYAVNGTEIL
60 70 80 90 100
LPCTFSSCFG FEDLHFRWTY NSSDAFKILI EGTVKNEKSD PKVTLKDDDR
110 120 130 140 150
ITLVGSTKEK MNNISIVLRD LEFSDTGKYT CHVKNPKENN LQHHATIFLQ
160 170 180 190 200
VVDRLEEVDN TVTLIILAVV GGVIGLLILI LLIKKLIIFI LKKTREKKKE
210 220
CLVSSSGNDN TENGLPGSKA EEKPPSKV
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 40 | D → Y in AAH35017 (PubMed:15489334).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_071317 | 162 | V → G in ATFB17. 1 PublicationCorresponds to variant dbSNP:rs587777559EnsemblClinVar. | 1 | |
Natural variantiVAR_071318 | 166 | I → L in ATFB17. 1 PublicationCorresponds to variant dbSNP:rs587777560EnsemblClinVar. | 1 | |
Natural variantiVAR_043488 | 179 | L → F in LQT10; increase in late sodium current. 1 PublicationCorresponds to variant dbSNP:rs121434386EnsemblClinVar. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_053913 | 1 – 110 | Missing in isoform 2. CuratedAdd BLAST | 110 | |
Alternative sequenceiVSP_046971 | 21 – 155 | GLFLL…VVDRL → V in isoform 3. CuratedAdd BLAST | 135 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AY149967 mRNA Translation: AAN74584.1 AP002800 Genomic DNA No translation available. BC035017 mRNA Translation: AAH35017.1 |
CCDSi | CCDS44744.1 [Q8IWT1-3] CCDS8389.1 [Q8IWT1-1] |
RefSeqi | NP_001135820.1, NM_001142348.1 [Q8IWT1-3] NP_001135821.1, NM_001142349.1 [Q8IWT1-2] NP_777594.1, NM_174934.3 [Q8IWT1-1] |
Genome annotation databases
Ensembli | ENST00000324727.9; ENSP00000322460.4; ENSG00000177098.9 ENST00000529878.1; ENSP00000436343.1; ENSG00000177098.9 [Q8IWT1-3] |
GeneIDi | 6330 |
KEGGi | hsa:6330 |
MANE-Selecti | ENST00000324727.9; ENSP00000322460.4; NM_174934.4; NP_777594.1 |
UCSCi | uc001pse.4, human [Q8IWT1-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AY149967 mRNA Translation: AAN74584.1 AP002800 Genomic DNA No translation available. BC035017 mRNA Translation: AAH35017.1 |
CCDSi | CCDS44744.1 [Q8IWT1-3] CCDS8389.1 [Q8IWT1-1] |
RefSeqi | NP_001135820.1, NM_001142348.1 [Q8IWT1-3] NP_001135821.1, NM_001142349.1 [Q8IWT1-2] NP_777594.1, NM_174934.3 [Q8IWT1-1] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
4MZ2 | X-ray | 1.72 | A | 32-157 | [»] | |
4MZ3 | X-ray | 1.74 | A/B | 32-157 | [»] | |
5XAW | X-ray | 2.10 | A/B | 30-152 | [»] | |
6VSV | X-ray | 1.62 | A | 32-157 | [»] | |
7DTD | electron microscopy | 3.30 | B | 1-228 | [»] | |
AlphaFoldDBi | Q8IWT1 | |||||
SMRi | Q8IWT1 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 112235, 5 interactors |
IntActi | Q8IWT1, 1 interactor |
STRINGi | 9606.ENSP00000322460 |
Chemistry databases
DrugBanki | DB05541, Brivaracetam DB00907, Cocaine DB13269, Dichlorobenzyl alcohol DB13961, Fish oil DB00776, Oxcarbazepine DB00243, Ranolazine DB00313, Valproic acid DB00909, Zonisamide |
DrugCentrali | Q8IWT1 |
Protein family/group databases
TCDBi | 8.A.17.2.2, the na(+) channel auxiliary subunit Beta1-Beta4 (sca-Beta) family |
PTM databases
GlyGeni | Q8IWT1, 3 sites |
iPTMneti | Q8IWT1 |
PhosphoSitePlusi | Q8IWT1 |
Genetic variation databases
BioMutai | SCN4B |
DMDMi | 57012701 |
Proteomic databases
jPOSTi | Q8IWT1 |
MassIVEi | Q8IWT1 |
PaxDbi | Q8IWT1 |
PeptideAtlasi | Q8IWT1 |
PRIDEi | Q8IWT1 |
ProteomicsDBi | 22813 70889 [Q8IWT1-1] 70890 [Q8IWT1-2] |
Protocols and materials databases
Antibodypediai | 2645, 142 antibodies from 27 providers |
DNASUi | 6330 |
Genome annotation databases
Ensembli | ENST00000324727.9; ENSP00000322460.4; ENSG00000177098.9 ENST00000529878.1; ENSP00000436343.1; ENSG00000177098.9 [Q8IWT1-3] |
GeneIDi | 6330 |
KEGGi | hsa:6330 |
MANE-Selecti | ENST00000324727.9; ENSP00000322460.4; NM_174934.4; NP_777594.1 |
UCSCi | uc001pse.4, human [Q8IWT1-1] |
Organism-specific databases
CTDi | 6330 |
DisGeNETi | 6330 |
GeneCardsi | SCN4B |
GeneReviewsi | SCN4B |
HGNCi | HGNC:10592, SCN4B |
HPAi | ENSG00000177098, Tissue enhanced (brain, tongue) |
MalaCardsi | SCN4B |
MIMi | 608256, gene 611819, phenotype |
neXtProti | NX_Q8IWT1 |
OpenTargetsi | ENSG00000177098 |
Orphaneti | 334, Familial atrial fibrillation 101016, Romano-Ward syndrome |
PharmGKBi | PA35007 |
VEuPathDBi | HostDB:ENSG00000177098 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | ENOG502QTZ6, Eukaryota |
GeneTreei | ENSGT01030000234556 |
HOGENOMi | CLU_104235_0_0_1 |
InParanoidi | Q8IWT1 |
OMAi | EGQYICF |
PhylomeDBi | Q8IWT1 |
TreeFami | TF331728 |
Enzyme and pathway databases
PathwayCommonsi | Q8IWT1 |
Reactomei | R-HSA-445095, Interaction between L1 and Ankyrins R-HSA-5576892, Phase 0 - rapid depolarisation R-HSA-9717207, Sensory perception of sweet, bitter, and umami (glutamate) taste |
SignaLinki | Q8IWT1 |
Miscellaneous databases
BioGRID-ORCSi | 6330, 8 hits in 1068 CRISPR screens |
ChiTaRSi | SCN4B, human |
GeneWikii | SCN4B |
GenomeRNAii | 6330 |
Pharosi | Q8IWT1, Tbio |
PROi | PR:Q8IWT1 |
RNActi | Q8IWT1, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000177098, Expressed in caudate nucleus and 192 other tissues |
ExpressionAtlasi | Q8IWT1, baseline and differential |
Genevisiblei | Q8IWT1, HS |
Family and domain databases
Gene3Di | 2.60.40.10, 1 hit |
InterProi | View protein in InterPro IPR007110, Ig-like_dom IPR036179, Ig-like_dom_sf IPR013783, Ig-like_fold IPR003599, Ig_sub IPR013106, Ig_V-set IPR000920, Myelin_P0-rel IPR044572, Na_channel_b4 |
PANTHERi | PTHR13869, PTHR13869, 1 hit PTHR13869:SF14, PTHR13869:SF14, 1 hit |
Pfami | View protein in Pfam PF07686, V-set, 1 hit |
SMARTi | View protein in SMART SM00409, IG, 1 hit |
SUPFAMi | SSF48726, SSF48726, 1 hit |
PROSITEi | View protein in PROSITE PS50835, IG_LIKE, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | SCN4B_HUMAN | |
Accessioni | Q8IWT1Primary (citable) accession number: Q8IWT1 Secondary accession number(s): E9PPT5, Q6PIG5 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | January 4, 2005 |
Last sequence update: | March 1, 2003 | |
Last modified: | May 25, 2022 | |
This is version 158 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Human chromosome 11
Human chromosome 11: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families