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O60939 (SCN2B_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 132. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Sodium channel subunit beta-2
Gene names
Name:SCN2B
ORF Names:UNQ326/PRO386
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length215 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Crucial in the assembly, expression, and functional modulation of the heterotrimeric complex of the sodium channel. The subunit beta-2 causes an increase in the plasma membrane surface area and in its folding into microvilli. Interacts with TNR may play a crucial role in clustering and regulation of activity of sodium channels at nodes of Ranvier By similarity.

Subunit structure

The voltage-sensitive sodium channel consists of an ion conducting pore forming alpha-subunit regulated by one or more beta-1, beta-2, beta-3 and/or beta-4 subunits. Beta-1 and beta-3 are non-covalently associated with alpha, while beta-2 and beta-4 are covalently linked by disulfide bonds By similarity. Ref.7

Subcellular location

Membrane; Single-pass type I membrane protein.

Tissue specificity

Brain specific.

Involvement in disease

Atrial fibrillation, familial, 14 (ATFB14) [MIM:615378]: A 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.8

Genetic variations in SCN2B may be involved in Brugada syndrome (Ref.9). This tachyarrhythmia is 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.

Sequence similarities

Belongs to the sodium channel auxiliary subunit SCN2B (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 componentMembrane
   Coding sequence diversityPolymorphism
   DiseaseAtrial fibrillation
Brugada syndrome
Disease mutation
   DomainImmunoglobulin domain
Signal
Transmembrane
Transmembrane helix
   LigandSodium
   Molecular functionIon channel
Sodium channel
Voltage-gated channel
   PTMDisulfide bond
Glycoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcardiac muscle cell action potential involved in contraction

Inferred from mutant phenotype Ref.8. Source: BHF-UCL

cardiac muscle contraction

Inferred from mutant phenotype Ref.8. Source: BHF-UCL

membrane depolarization during cardiac muscle cell action potential

Inferred from mutant phenotype Ref.8. Source: GOC

nervous system development

Inferred from electronic annotation. Source: Ensembl

regulation of atrial cardiac muscle cell membrane depolarization

Inferred from mutant phenotype Ref.8. Source: BHF-UCL

regulation of heart rate by cardiac conduction

Inferred from mutant phenotype Ref.8. Source: BHF-UCL

regulation of sodium ion transmembrane transporter activity

Inferred from direct assay Ref.8. Source: BHF-UCL

response to pyrethroid

Inferred from electronic annotation. Source: Ensembl

sodium ion transmembrane transport

Inferred from direct assay Ref.8. Source: BHF-UCL

synaptic transmission

Traceable author statement Ref.1. Source: ProtInc

   Cellular_componentvoltage-gated sodium channel complex

Traceable author statement Ref.1. Source: UniProtKB

   Molecular_functionsodium channel regulator activity

Inferred from direct assay Ref.8. Source: BHF-UCL

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

Inferred from mutant phenotype Ref.8. Source: BHF-UCL

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2929 By similarity
Chain30 – 215186Sodium channel subunit beta-2
PRO_0000014931

Regions

Topological domain30 – 159130Extracellular Potential
Transmembrane160 – 18021Helical; Potential
Topological domain181 – 21535Cytoplasmic Potential
Domain32 – 154123Ig-like C2-type

Amino acid modifications

Glycosylation421N-linked (GlcNAc...) Potential
Glycosylation661N-linked (GlcNAc...) Potential
Glycosylation741N-linked (GlcNAc...) Potential
Disulfide bond50 ↔ 127 Ref.7
Disulfide bond55Interchain; with alpha subunit Ref.7

Natural variations

Natural variant281R → Q in ATFB14; the mutant results in reduced sodium currents and altered channel gating when coexpressed with SCN5A in a heterologous expression system. Ref.8
VAR_070229
Natural variant281R → W in ATFB14; the mutant results in reduced sodium currents and altered channel gating when coexpressed with SCN5A in a heterologous expression system. Ref.8
Corresponds to variant rs17121819 [ dbSNP | Ensembl ].
VAR_029131
Natural variant471R → H.
Corresponds to variant rs17121818 [ dbSNP | Ensembl ].
VAR_029132
Natural variant2111D → G Found in a patient with Brugada syndrome; unknown pathological significance; induces a reduction in sodium current density most likely by decreasing SCN5A protein cell surface expression. Ref.9
VAR_070230

Experimental info

Sequence conflict21H → Q in AAC26013. Ref.1
Sequence conflict81P → L in AAC26013. Ref.1
Sequence conflict151T → N in AAC26013. Ref.1
Sequence conflict481L → Q in AAC26013. Ref.1
Sequence conflict681T → S in AAC26013. Ref.1
Sequence conflict1561S → F in AAD47196. Ref.3
Sequence conflict178 – 1792MV → TA in AAC26013. Ref.1

Sequences

Sequence LengthMass (Da)Tools
O60939 [UniParc].

Last modified August 1, 1998. Version 1.
Checksum: 94A30A60A32683F3

FASTA21524,326
        10         20         30         40         50         60 
MHRDAWLPRP AFSLTGLSLF FSLVPPGRSM EVTVPATLNV LNGSDARLPC TFNSCYTVNH 

        70         80         90        100        110        120 
KQFSLNWTYQ ECNNCSEEMF LQFRMKIINL KLERFQDRVE FSGNPSKYDV SVMLRNVQPE 

       130        140        150        160        170        180 
DEGIYNCYIM NPPDRHRGHG KIHLQVLMEE PPERDSTVAV IVGASVGGFL AVVILVLMVV 

       190        200        210 
KCVRRKKEQK LSTDDLKTEE EGKTDGEGNP DDGAK 

« Hide

References

« Hide 'large scale' references
[1]"Structure and chromosomal localization of the beta2 subunit of the human brain sodium channel."
Eubanks J., Srinivasan J., Dinulos M.B., Disteche C.M., Catterall W.A.
NeuroReport 8:2775-2779(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Brain.
[2]"Exclusion of the SCN2B gene as candidate for CMT4B."
Bolino A., Seri M., Caroli F., Eubanks J., Srinivasan J., Mandich P., Schenone A., Quattrone A., Romeo G., Catterall W.A., Devoto M.
Eur. J. Hum. Genet. 6:629-634(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Tissue: Brain.
[3]"Whether 'slip-mode conductance' occurs."
Cruz J.S., Santana L.F., Frederick C.A., Isom L.L., Malhotra J.D., Mattei L.N., Kass R.S., Xia J., An R.-H., Lederer W.J.
Science 284:711-711(1999)
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Heart.
[4]"Primary structure and functional expression of a beta 2 subunit of human infant brain sodium channels."
Isom L.L., Mattei L.N., Ragsdale D.S.
Submitted (JAN-1997) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[5]"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment."
Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. expand/collapse author list , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.
Genome Res. 13:2265-2270(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[6]"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: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Brain.
[7]"Identification of the cysteine residue responsible for disulfide linkage of Na+ channel alpha and beta2 subunits."
Chen C., Calhoun J.D., Zhang Y., Lopez-Santiago L., Zhou N., Davis T.H., Salzer J.L., Isom L.L.
J. Biol. Chem. 287:39061-39069(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBUNIT, DISULFIDE BONDS.
[8]"Mutations in sodium channel beta1- and beta2-subunits associated with atrial fibrillation."
Watanabe H., Darbar D., Kaiser D.W., Jiramongkolchai K., Chopra S., Donahue B.S., Kannankeril P.J., Roden D.M.
Circ. Arrhythm. Electrophysiol. 2:268-275(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS ATFB14 GLN-28 AND TRP-28, CHARACTERIZATION OF VARIANTS ATFB14 GLN-28 AND TRP-28.
[9]"A missense mutation in the sodium channel beta2 subunit reveals SCN2B as a new candidate gene for Brugada syndrome."
Riuro H., Beltran-Alvarez P., Tarradas A., Selga E., Campuzano O., Verges M., Pagans S., Iglesias A., Brugada J., Brugada P., Vazquez F.M., Perez G.J., Scornik F.S., Brugada R.
Hum. Mutat. 34:961-966(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT GLY-211, CHARACTERIZATION OF VARIANT GLY-211, POSSIBLE INVOLVEMENT IN BRUGADA SYNDROME.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF007783 mRNA. Translation: AAC26013.1.
AF049498 mRNA. Translation: AAC05274.1.
AF049497, AF049496 Genomic DNA. Translation: AAC05208.1.
AF107028 mRNA. Translation: AAD47196.1.
U87555 mRNA. Translation: AAF21472.1.
AY358945 mRNA. Translation: AAQ89304.1.
BC036793 mRNA. Translation: AAH36793.1.
CCDSCCDS8390.1.
RefSeqNP_004579.1. NM_004588.4.
UniGeneHs.129783.

3D structure databases

ProteinModelPortalO60939.
SMRO60939. Positions 35-129.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9606.ENSP00000278947.

Chemistry

BindingDBO60939.

Protein family/group databases

TCDB8.A.17.2.1. the na(+) channel auxiliary subunit 1-4 (sca-) family.

PTM databases

PhosphoSiteO60939.

Proteomic databases

PaxDbO60939.
PeptideAtlasO60939.
PRIDEO60939.

Protocols and materials databases

DNASU6327.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000278947; ENSP00000278947; ENSG00000149575.
GeneID6327.
KEGGhsa:6327.
UCSCuc001psf.2. human.

Organism-specific databases

CTD6327.
GeneCardsGC11M118033.
HGNCHGNC:10589. SCN2B.
HPAHPA012585.
MIM601327. gene.
615378. phenotype.
neXtProtNX_O60939.
Orphanet334. Familial atrial fibrillation.
PharmGKBPA303.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG26453.
HOGENOMHOG000118120.
HOVERGENHBG003443.
InParanoidO60939.
KOK04846.
OMAHGKIYLQ.
OrthoDBEOG7NSB42.
PhylomeDBO60939.
TreeFamTF331728.

Enzyme and pathway databases

ReactomeREACT_111045. Developmental Biology.

Gene expression databases

ArrayExpressO60939.
BgeeO60939.
CleanExHS_SCN2B.
GenevestigatorO60939.

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.
IPR000920. Myelin_P0.
[Graphical view]
PfamPF07686. V-set. 1 hit.
[Graphical view]
PRINTSPR00213. MYELINP0.
SMARTSM00409. IG. 1 hit.
[Graphical view]
PROSITEPS50835. IG_LIKE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiSCN2B.
GenomeRNAi6327.
NextBio24558.
PMAP-CutDBO60939.
PROO60939.
SOURCESearch...

Entry information

Entry nameSCN2B_HUMAN
AccessionPrimary (citable) accession number: O60939
Secondary accession number(s): O75302, Q9UNN3
Entry history
Integrated into UniProtKB/Swiss-Prot: January 11, 2001
Last sequence update: August 1, 1998
Last modified: July 9, 2014
This is version 132 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

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