Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q8IWT1 (SCN4B_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 103. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Sodium channel subunit beta-4
Gene names
Name:SCN4B
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length228 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.4

Subunit structure

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. Ref.4

Subcellular location

Cell membrane; Single-pass type I membrane protein Ref.4.

Tissue specificity

Expressed at a high level in dorsal root ganglia, at a lower level in brain, spinal cord, skeletal muscle and heart. Ref.1

Post-translational modification

Contains an interchain disulfide bond with SCN2A.

N-glycosylated. Ref.4

Involvement in disease

Long QT syndrome 10 (LQT10) [MIM:611819]: A 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.5

Sequence similarities

Belongs to the sodium channel auxiliary subunit SCN4B (TC 8.A.17) family. [View classification]

Contains 1 Ig-like C2-type (immunoglobulin-like) domain.

Ontologies

Keywords
   Biological processIon transport
Sodium transport
Transport
   Cellular componentCell membrane
Membrane
   Coding sequence diversityAlternative splicing
   DiseaseDisease mutation
Long QT syndrome
   DomainImmunoglobulin domain
Signal
Transmembrane
Transmembrane helix
   LigandSodium
   Molecular functionIon channel
Sodium channel
Voltage-gated channel
   PTMDisulfide bond
Glycoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processAV node cell to bundle of His cell communication

Inferred from mutant phenotype Ref.5. Source: BHF-UCL

cardiac muscle cell action potential involved in contraction

Inferred from mutant phenotype Ref.5. Source: BHF-UCL

cardiac muscle contraction

Inferred from mutant phenotype Ref.5. Source: BHF-UCL

membrane depolarization during cardiac muscle cell action potential

Inferred from mutant phenotype Ref.5. Source: BHF-UCL

positive regulation of sodium ion transport

Inferred from direct assay Ref.5. Source: BHF-UCL

regulation of heart rate by cardiac conduction

Inferred from mutant phenotype Ref.5. Source: BHF-UCL

regulation of sodium ion transmembrane transporter activity

Inferred from direct assay Ref.4. Source: UniProtKB

regulation of ventricular cardiac muscle cell membrane repolarization

Inferred from mutant phenotype Ref.5. Source: BHF-UCL

sodium ion transmembrane transport

Inferred from direct assay PubMed 20226894. Source: BHF-UCL

sodium ion transport

Inferred from direct assay Ref.1. Source: UniProtKB

   Cellular_componentintercalated disc

Inferred from sequence or structural similarity. Source: BHF-UCL

intrinsic component of plasma membrane

Inferred from direct assay Ref.4. Source: UniProtKB

voltage-gated sodium channel complex

Inferred from direct assay Ref.1. Source: UniProtKB

   Molecular_functionion channel binding

Inferred from physical interaction Ref.5. Source: BHF-UCL

sodium channel regulator activity

Inferred from direct assay Ref.4. Source: UniProtKB

voltage-gated sodium channel activity

Inferred from direct assay Ref.1. Source: UniProtKB

voltage-gated sodium channel activity involved in cardiac muscle cell action potential

Inferred from mutant phenotype Ref.5. Source: BHF-UCL

Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q8IWT1-1)

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.
Isoform 2 (identifier: Q8IWT1-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-110: Missing.
Note: No experimental confirmation available.
Isoform 3 (identifier: Q8IWT1-3)

The sequence of this isoform differs from the canonical sequence as follows:
     21-155: GLFLLPVTLS...TIFLQVVDRL → V
Note: Gene prediction based on EST data.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 3030 Potential
Chain31 – 228198Sodium channel subunit beta-4
PRO_0000014937

Regions

Topological domain31 – 162132Extracellular Potential
Transmembrane163 – 18321Helical; Potential
Topological domain184 – 22845Cytoplasmic Potential
Domain31 – 148118Ig-like C2-type

Amino acid modifications

Glycosylation451N-linked (GlcNAc...) Potential
Glycosylation711N-linked (GlcNAc...) Potential
Glycosylation1131N-linked (GlcNAc...) Potential
Disulfide bond53 ↔ 131 Ref.4
Disulfide bond58Interchain; with alpha subunit Ref.4

Natural variations

Alternative sequence1 – 110110Missing in isoform 2.
VSP_053913
Alternative sequence21 – 155135GLFLL…VVDRL → V in isoform 3.
VSP_046971
Natural variant1791L → F in LQT10; increase in late sodium current. Ref.5
VAR_043488

Experimental info

Mutagenesis581C → A: Abolishes regulation of channel activity. Ref.4
Mutagenesis1311C → A or W: Decreases protein stability. Causes conformation changes that impair interaction with the alpha subunit. Ref.4
Sequence conflict401D → Y in AAH35017. Ref.3

Secondary structure

.......................... 228
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified March 1, 2003. Version 1.
Checksum: 2F17E1210E8EFEF8

FASTA22824,969
        10         20         30         40         50         60 
MPGAGDGGKA PARWLGTGLL GLFLLPVTLS LEVSVGKATD IYAVNGTEIL LPCTFSSCFG 

        70         80         90        100        110        120 
FEDLHFRWTY NSSDAFKILI EGTVKNEKSD PKVTLKDDDR ITLVGSTKEK MNNISIVLRD 

       130        140        150        160        170        180 
LEFSDTGKYT CHVKNPKENN LQHHATIFLQ VVDRLEEVDN TVTLIILAVV GGVIGLLILI 

       190        200        210        220 
LLIKKLIIFI LKKTREKKKE CLVSSSGNDN TENGLPGSKA EEKPPSKV 

« Hide

Isoform 2 [UniParc].

Checksum: 171185D98FAB28ED
Show »

FASTA11813,104
Isoform 3 [UniParc].

Checksum: 5E474827FFA2FA01
Show »

FASTA949,876

References

« Hide 'large scale' references
[1]"Sodium channel beta4, a new disulfide-linked auxiliary subunit with similarity to beta2."
Yu F.H., Westenbroek R.E., Silos-Santiago I., McCormick K.A., Lawson D., Ge P., Ferriera H., Lilly J., DiStefano P.S., Catterall W.A., Scheuer T., Curtis R.
J. Neurosci. 23:7577-7585(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY.
Tissue: Brain.
[2]"Human chromosome 11 DNA sequence and analysis including novel gene identification."
Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. expand/collapse author list , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y.
Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: PARTIAL NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Brain.
[4]"Crystallographic insights into sodium-channel modulation by the beta4 subunit."
Gilchrist J., Das S., Van Petegem F., Bosmans F.
Proc. Natl. Acad. Sci. U.S.A. 110:E5016-E5024(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.72 ANGSTROMS) OF 32-157, FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, DISULFIDE BOND, GLYCOSYLATION, INTERACTION WITH SCN2A, MUTAGENESIS OF CYS-58 AND CYS-131.
[5]"SCN4B-encoded sodium channel beta4 subunit in congenital long-QT syndrome."
Medeiros-Domingo A., Kaku T., Tester D.J., Iturralde-Torres P., Itty A., Ye B., Valdivia C., Ueda K., Canizales-Quinteros S., Tusie-Luna M.T., Makielski J.C., Ackerman M.J.
Circulation 116:134-142(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT LQT10 PHE-179, CHARACTERIZATION OF VARIANT LQT10 PHE-179.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AY149967 mRNA. Translation: AAN74584.1.
AP002800 Genomic DNA. No translation available.
BC035017 mRNA. Translation: AAH35017.1.
CCDSCCDS44744.1. [Q8IWT1-3]
CCDS8389.1. [Q8IWT1-1]
RefSeqNP_001135820.1. NM_001142348.1. [Q8IWT1-3]
NP_001135821.1. NM_001142349.1. [Q8IWT1-2]
NP_777594.1. NM_174934.3. [Q8IWT1-1]
UniGeneHs.65239.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
4MZ2X-ray1.72A32-157[»]
4MZ3X-ray1.74A/B32-157[»]
ProteinModelPortalQ8IWT1.
SMRQ8IWT1. Positions 36-155.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid112235. 1 interaction.
STRING9606.ENSP00000322460.

Chemistry

BindingDBQ8IWT1.

Protein family/group databases

TCDB8.A.17.2.2. the na(+) channel auxiliary subunit 1-4 (sca-) family.

PTM databases

PhosphoSiteQ8IWT1.

Polymorphism databases

DMDM57012701.

Proteomic databases

PaxDbQ8IWT1.
PRIDEQ8IWT1.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000324727; ENSP00000322460; ENSG00000177098. [Q8IWT1-1]
ENST00000529878; ENSP00000436343; ENSG00000177098. [Q8IWT1-3]
GeneID6330.
KEGGhsa:6330.
UCSCuc001pse.3. human. [Q8IWT1-1]

Organism-specific databases

CTD6330.
GeneCardsGC11M118004.
GeneReviewsSCN4B.
HGNCHGNC:10592. SCN4B.
HPAHPA017293.
MIM608256. gene.
611819. phenotype.
neXtProtNX_Q8IWT1.
Orphanet101016. Romano-Ward syndrome.
PharmGKBPA35007.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG46712.
HOGENOMHOG000048715.
HOVERGENHBG056581.
InParanoidQ8IWT1.
KOK04848.
OMAREKKKEC.
OrthoDBEOG7WT42T.
PhylomeDBQ8IWT1.
TreeFamTF331728.

Gene expression databases

ArrayExpressQ8IWT1.
BgeeQ8IWT1.
CleanExHS_SCN4B.
GenevestigatorQ8IWT1.

Family and domain databases

Gene3D2.60.40.10. 1 hit.
InterProIPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003599. Ig_sub.
IPR013106. Ig_V-set.
[Graphical view]
PfamPF07686. V-set. 1 hit.
[Graphical view]
SMARTSM00409. IG. 1 hit.
[Graphical view]
PROSITEPS50835. IG_LIKE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiSCN4B.
GenomeRNAi6330.
NextBio24574.
PMAP-CutDBQ8IWT1.
PROQ8IWT1.
SOURCESearch...

Entry information

Entry nameSCN4B_HUMAN
AccessionPrimary (citable) accession number: Q8IWT1
Secondary accession number(s): E9PPT5, Q6PIG5
Entry history
Integrated into UniProtKB/Swiss-Prot: January 4, 2005
Last sequence update: March 1, 2003
Last modified: July 9, 2014
This is version 103 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 11

Human chromosome 11: entries, gene names and cross-references to MIM