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Protein

Sodium channel subunit beta-4

Gene

SCN4B

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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 suceptibility of the sodium channel to inhibition by toxic peptides from spider, scorpion, wasp and sea anemone venom.1 Publication

GO - Molecular functioni

  • ion channel binding Source: BHF-UCL
  • sodium channel regulator activity Source: UniProtKB
  • 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
Complete GO annotation...

Keywords - Molecular functioni

Ion channel, Sodium channel, Voltage-gated channel

Keywords - Biological processi

Ion transport, Sodium transport, Transport

Keywords - Ligandi

Sodium

Enzyme and pathway databases

ReactomeiR-HSA-445095. Interaction between L1 and Ankyrins.
R-HSA-5576892. Phase 0 - rapid depolarisation.

Protein family/group databases

TCDBi8.A.17.2.2. the na(+) channel auxiliary subunit 1-4 (sca-) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Sodium channel subunit beta-4
Gene namesi
Name:SCN4B
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

HGNCiHGNC:10592. SCN4B.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini31 – 162ExtracellularSequence analysisAdd BLAST132
Transmembranei163 – 183HelicalSequence analysisAdd BLAST21
Topological domaini184 – 228CytoplasmicSequence analysisAdd BLAST45

GO - Cellular componenti

  • intercalated disc Source: BHF-UCL
  • intrinsic component of plasma membrane Source: UniProtKB
  • voltage-gated sodium channel complex Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Involvement in diseasei

Long QT syndrome 10 (LQT10)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA heart disorder characterized by a prolonged QT interval on the ECG and polymorphic ventricular arrhythmias. They cause syncope and sudden death in response to exercise or emotional stress, and can present with a sentinel event of sudden cardiac death in infancy.
See also OMIM:611819
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_043488179L → F in LQT10; increase in late sodium current. 1 PublicationCorresponds to variant rs121434386dbSNPEnsembl.1
Atrial fibrillation, familial, 17 (ATFB17)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease 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 also OMIM:611819
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_071317162V → G in ATFB17. 1 PublicationCorresponds to variant rs587777559dbSNPEnsembl.1
Natural variantiVAR_071318166I → L in ATFB17. 1 PublicationCorresponds to variant rs587777560dbSNPEnsembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi58C → A: Abolishes regulation of channel activity. 1 Publication1
Mutagenesisi131C → A or W: Decreases protein stability. Causes conformation changes that impair interaction with the alpha subunit. 1 Publication1

Keywords - Diseasei

Atrial fibrillation, Disease mutation, Long QT syndrome

Organism-specific databases

DisGeNETi6330.
MalaCardsiSCN4B.
MIMi611819. phenotype.
OpenTargetsiENSG00000177098.
Orphaneti334. Familial atrial fibrillation.
101016. Romano-Ward syndrome.
PharmGKBiPA35007.

Chemistry databases

DrugBankiDB00313. Valproic Acid.
DB00909. Zonisamide.

Polymorphism and mutation databases

BioMutaiSCN4B.
DMDMi57012701.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 30Sequence analysisAdd BLAST30
ChainiPRO_000001493731 – 228Sodium channel subunit beta-4Add BLAST198

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi45N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi53 ↔ 131PROSITE-ProRule annotation1 Publication
Disulfide bondi58Interchain; with alpha subunitPROSITE-ProRule annotation1 Publication
Glycosylationi71N-linked (GlcNAc...)Sequence analysis1
Glycosylationi113N-linked (GlcNAc...)Sequence analysis1

Post-translational modificationi

Contains an interchain disulfide bond with SCN2A.
N-glycosylated.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ8IWT1.
PeptideAtlasiQ8IWT1.
PRIDEiQ8IWT1.

PTM databases

iPTMnetiQ8IWT1.
PhosphoSitePlusiQ8IWT1.

Miscellaneous databases

PMAP-CutDBQ8IWT1.

Expressioni

Tissue specificityi

Expressed at a high level in dorsal root ganglia, at a lower level in brain, spinal cord, skeletal muscle and heart. Expressed in the atrium.2 Publications

Gene expression databases

BgeeiENSG00000177098.
CleanExiHS_SCN4B.
ExpressionAtlasiQ8IWT1. baseline and differential.
GenevisibleiQ8IWT1. HS.

Organism-specific databases

HPAiHPA017293.

Interactioni

Subunit structurei

Component of the voltage-sensitive sodium channel complex that consists of an ion-conducting pore-forming alpha subunit and one or more regulatory beta subunits. Heterooligomer with SCN2A; disulfide-linked.1 Publication

GO - Molecular functioni

  • ion channel binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi112235. 1 interactor.
STRINGi9606.ENSP00000322460.

Structurei

Secondary structure

1228
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi40 – 44Combined sources5
Beta strandi49 – 51Combined sources3
Turni58 – 60Combined sources3
Beta strandi62 – 71Combined sources10
Beta strandi76 – 86Combined sources11
Beta strandi92 – 96Combined sources5
Beta strandi101 – 103Combined sources3
Beta strandi116 – 118Combined sources3
Helixi123 – 125Combined sources3
Beta strandi127 – 135Combined sources9
Helixi136 – 138Combined sources3
Beta strandi140 – 143Combined sources4
Beta strandi147 – 152Combined sources6

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4MZ2X-ray1.72A32-157[»]
4MZ3X-ray1.74A/B32-157[»]
ProteinModelPortaliQ8IWT1.
SMRiQ8IWT1.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini31 – 148Ig-like C2-typeAdd BLAST118

Sequence similaritiesi

Keywords - Domaini

Immunoglobulin domain, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IXQZ. Eukaryota.
ENOG4111PJ2. LUCA.
GeneTreeiENSGT00640000091161.
HOGENOMiHOG000048715.
HOVERGENiHBG056581.
InParanoidiQ8IWT1.
KOiK04848.
OMAiREKKKEC.
OrthoDBiEOG091G0MQV.
PhylomeDBiQ8IWT1.
TreeFamiTF331728.

Family and domain databases

Gene3Di2.60.40.10. 1 hit.
InterProiIPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003599. Ig_sub.
IPR013106. Ig_V-set.
IPR000920. Myelin_P0-rel.
[Graphical view]
PANTHERiPTHR13869. PTHR13869. 1 hit.
PfamiPF07686. V-set. 1 hit.
[Graphical view]
SMARTiSM00409. IG. 1 hit.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 1 hit.
PROSITEiPS50835. IG_LIKE. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q8IWT1-1) [UniParc]FASTAAdd to basket

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.

« Hide

        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
Length:228
Mass (Da):24,969
Last modified:March 1, 2003 - v1
Checksum:i2F17E1210E8EFEF8
GO
Isoform 2 (identifier: Q8IWT1-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-110: Missing.

Note: No experimental confirmation available.
Show »
Length:118
Mass (Da):13,104
Checksum:i171185D98FAB28ED
GO
Isoform 3 (identifier: Q8IWT1-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     21-155: GLFLLPVTLS...TIFLQVVDRL → V

Note: Gene prediction based on EST data.
Show »
Length:94
Mass (Da):9,876
Checksum:i5E474827FFA2FA01
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti40D → Y in AAH35017 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_071317162V → G in ATFB17. 1 PublicationCorresponds to variant rs587777559dbSNPEnsembl.1
Natural variantiVAR_071318166I → L in ATFB17. 1 PublicationCorresponds to variant rs587777560dbSNPEnsembl.1
Natural variantiVAR_043488179L → F in LQT10; increase in late sodium current. 1 PublicationCorresponds to variant rs121434386dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0539131 – 110Missing in isoform 2. CuratedAdd BLAST110
Alternative sequenceiVSP_04697121 – 155GLFLL…VVDRL → V in isoform 3. CuratedAdd BLAST135

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.
CCDSiCCDS44744.1. [Q8IWT1-3]
CCDS8389.1. [Q8IWT1-1]
RefSeqiNP_001135820.1. NM_001142348.1. [Q8IWT1-3]
NP_001135821.1. NM_001142349.1. [Q8IWT1-2]
NP_777594.1. NM_174934.3. [Q8IWT1-1]
UniGeneiHs.65239.

Genome annotation databases

EnsembliENST00000324727; ENSP00000322460; ENSG00000177098. [Q8IWT1-1]
ENST00000529878; ENSP00000436343; ENSG00000177098. [Q8IWT1-3]
GeneIDi6330.
KEGGihsa:6330.
UCSCiuc001pse.4. human. [Q8IWT1-1]

Keywords - Coding sequence diversityi

Alternative splicing

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.
CCDSiCCDS44744.1. [Q8IWT1-3]
CCDS8389.1. [Q8IWT1-1]
RefSeqiNP_001135820.1. NM_001142348.1. [Q8IWT1-3]
NP_001135821.1. NM_001142349.1. [Q8IWT1-2]
NP_777594.1. NM_174934.3. [Q8IWT1-1]
UniGeneiHs.65239.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4MZ2X-ray1.72A32-157[»]
4MZ3X-ray1.74A/B32-157[»]
ProteinModelPortaliQ8IWT1.
SMRiQ8IWT1.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112235. 1 interactor.
STRINGi9606.ENSP00000322460.

Chemistry databases

DrugBankiDB00313. Valproic Acid.
DB00909. Zonisamide.

Protein family/group databases

TCDBi8.A.17.2.2. the na(+) channel auxiliary subunit 1-4 (sca-) family.

PTM databases

iPTMnetiQ8IWT1.
PhosphoSitePlusiQ8IWT1.

Polymorphism and mutation databases

BioMutaiSCN4B.
DMDMi57012701.

Proteomic databases

PaxDbiQ8IWT1.
PeptideAtlasiQ8IWT1.
PRIDEiQ8IWT1.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000324727; ENSP00000322460; ENSG00000177098. [Q8IWT1-1]
ENST00000529878; ENSP00000436343; ENSG00000177098. [Q8IWT1-3]
GeneIDi6330.
KEGGihsa:6330.
UCSCiuc001pse.4. human. [Q8IWT1-1]

Organism-specific databases

CTDi6330.
DisGeNETi6330.
GeneCardsiSCN4B.
GeneReviewsiSCN4B.
HGNCiHGNC:10592. SCN4B.
HPAiHPA017293.
MalaCardsiSCN4B.
MIMi608256. gene.
611819. phenotype.
neXtProtiNX_Q8IWT1.
OpenTargetsiENSG00000177098.
Orphaneti334. Familial atrial fibrillation.
101016. Romano-Ward syndrome.
PharmGKBiPA35007.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IXQZ. Eukaryota.
ENOG4111PJ2. LUCA.
GeneTreeiENSGT00640000091161.
HOGENOMiHOG000048715.
HOVERGENiHBG056581.
InParanoidiQ8IWT1.
KOiK04848.
OMAiREKKKEC.
OrthoDBiEOG091G0MQV.
PhylomeDBiQ8IWT1.
TreeFamiTF331728.

Enzyme and pathway databases

ReactomeiR-HSA-445095. Interaction between L1 and Ankyrins.
R-HSA-5576892. Phase 0 - rapid depolarisation.

Miscellaneous databases

ChiTaRSiSCN4B. human.
GeneWikiiSCN4B.
GenomeRNAii6330.
PMAP-CutDBQ8IWT1.
PROiQ8IWT1.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000177098.
CleanExiHS_SCN4B.
ExpressionAtlasiQ8IWT1. baseline and differential.
GenevisibleiQ8IWT1. HS.

Family and domain databases

Gene3Di2.60.40.10. 1 hit.
InterProiIPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003599. Ig_sub.
IPR013106. Ig_V-set.
IPR000920. Myelin_P0-rel.
[Graphical view]
PANTHERiPTHR13869. PTHR13869. 1 hit.
PfamiPF07686. V-set. 1 hit.
[Graphical view]
SMARTiSM00409. IG. 1 hit.
[Graphical view]
SUPFAMiSSF48726. SSF48726. 1 hit.
PROSITEiPS50835. IG_LIKE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiSCN4B_HUMAN
AccessioniPrimary (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: November 2, 2016
This is version 125 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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, Complete proteome, Reference proteome

Documents

  1. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.