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Sodium channel subunit beta-2

 SCN2B_HUMAN             Reviewed;         215 AA.
O60939; O75302; Q9UNN3;
11-JAN-2001, integrated into UniProtKB/Swiss-Prot.
01-AUG-1998, sequence version 1.
20-JUN-2018, entry version 164.
RecName: Full=Sodium channel subunit beta-2;
Flags: Precursor;
Name=SCN2B; ORFNames=UNQ326/PRO386;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [MRNA].
TISSUE=Brain;
PubMed=9295116; DOI=10.1097/00001756-199708180-00025;
Eubanks J., Srinivasan J., Dinulos M.B., Disteche C.M.,
Catterall W.A.;
"Structure and chromosomal localization of the beta2 subunit of the
human brain sodium channel.";
NeuroReport 8:2775-2779(1997).
[2]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
TISSUE=Brain;
PubMed=9887383; DOI=10.1038/sj.ejhg.5200220;
Bolino A., Seri M., Caroli F., Eubanks J., Srinivasan J., Mandich P.,
Schenone A., Quattrone A., Romeo G., Catterall W.A., Devoto M.;
"Exclusion of the SCN2B gene as candidate for CMT4B.";
Eur. J. Hum. Genet. 6:629-634(1998).
[3]
NUCLEOTIDE SEQUENCE [MRNA].
TISSUE=Heart;
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.;
"Whether 'slip-mode conductance' occurs.";
Science 284:711-711(1999).
[4]
NUCLEOTIDE SEQUENCE [MRNA].
Isom L.L., Mattei L.N., Ragsdale D.S.;
"Primary structure and functional expression of a beta 2 subunit of
human infant brain sodium channels.";
Submitted (JAN-1997) to the EMBL/GenBank/DDBJ databases.
[5]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
PubMed=12975309; DOI=10.1101/gr.1293003;
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., 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.;
"The secreted protein discovery initiative (SPDI), a large-scale
effort to identify novel human secreted and transmembrane proteins: a
bioinformatics assessment.";
Genome Res. 13:2265-2270(2003).
[6]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
TISSUE=Brain;
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[7]
SUBUNIT, AND DISULFIDE BONDS.
PubMed=22992729; DOI=10.1074/jbc.M112.397646;
Chen C., Calhoun J.D., Zhang Y., Lopez-Santiago L., Zhou N.,
Davis T.H., Salzer J.L., Isom L.L.;
"Identification of the cysteine residue responsible for disulfide
linkage of Na+ channel alpha and beta2 subunits.";
J. Biol. Chem. 287:39061-39069(2012).
[8]
VARIANTS ATFB14 GLN-28 AND TRP-28, AND CHARACTERIZATION OF VARIANTS
ATFB14 GLN-28 AND TRP-28.
PubMed=19808477; DOI=10.1161/CIRCEP.108.779181;
Watanabe H., Darbar D., Kaiser D.W., Jiramongkolchai K., Chopra S.,
Donahue B.S., Kannankeril P.J., Roden D.M.;
"Mutations in sodium channel beta1- and beta2-subunits associated with
atrial fibrillation.";
Circ. Arrhythm. Electrophysiol. 2:268-275(2009).
[9]
VARIANT GLY-211, CHARACTERIZATION OF VARIANT GLY-211, AND POSSIBLE
INVOLVEMENT IN BRUGADA SYNDROME.
PubMed=23559163; DOI=10.1002/humu.22328;
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.;
"A missense mutation in the sodium channel beta2 subunit reveals SCN2B
as a new candidate gene for Brugada syndrome.";
Hum. Mutat. 34:961-966(2013).
-!- 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).
{ECO:0000250}.
-!- SUBUNIT: 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).
{ECO:0000250}.
-!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane
protein.
-!- TISSUE SPECIFICITY: Brain specific.
-!- 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.
{ECO:0000269|PubMed:19808477}. Note=The disease is caused by
mutations affecting the gene represented in this entry.
-!- DISEASE: Note=Genetic variations in SCN2B may be involved in
Brugada syndrome (PubMed:23559163). 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. {ECO:0000269|PubMed:23559163}.
-!- SIMILARITY: Belongs to the sodium channel auxiliary subunit SCN2B
(TC 8.A.17) family. {ECO:0000305}.
-----------------------------------------------------------------------
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EMBL; AF007783; AAC26013.1; -; mRNA.
EMBL; AF049498; AAC05274.1; -; mRNA.
EMBL; AF049497; AAC05208.1; -; Genomic_DNA.
EMBL; AF049496; AAC05208.1; JOINED; Genomic_DNA.
EMBL; AF107028; AAD47196.1; -; mRNA.
EMBL; U87555; AAF21472.1; -; mRNA.
EMBL; AY358945; AAQ89304.1; -; mRNA.
EMBL; BC036793; AAH36793.1; -; mRNA.
CCDS; CCDS8390.1; -.
RefSeq; NP_004579.1; NM_004588.4.
UniGene; Hs.129783; -.
PDB; 5FDY; X-ray; 1.85 A; A/B=30-153.
PDB; 5FEB; X-ray; 1.35 A; A=30-151.
PDBsum; 5FDY; -.
PDBsum; 5FEB; -.
ProteinModelPortal; O60939; -.
SMR; O60939; -.
BioGrid; 112232; 87.
CORUM; O60939; -.
STRING; 9606.ENSP00000278947; -.
DrugBank; DB00313; Valproic Acid.
DrugBank; DB00909; Zonisamide.
TCDB; 8.A.17.2.1; the na(+) channel auxiliary subunit Beta1-Beta4 (sca-Beta) family.
iPTMnet; O60939; -.
PhosphoSitePlus; O60939; -.
BioMuta; SCN2B; -.
PaxDb; O60939; -.
PeptideAtlas; O60939; -.
PRIDE; O60939; -.
ProteomicsDB; 49682; -.
DNASU; 6327; -.
Ensembl; ENST00000278947; ENSP00000278947; ENSG00000149575.
GeneID; 6327; -.
KEGG; hsa:6327; -.
CTD; 6327; -.
DisGeNET; 6327; -.
EuPathDB; HostDB:ENSG00000149575.5; -.
GeneCards; SCN2B; -.
HGNC; HGNC:10589; SCN2B.
MalaCards; SCN2B; -.
MIM; 601327; gene.
MIM; 615378; phenotype.
neXtProt; NX_O60939; -.
OpenTargets; ENSG00000149575; -.
Orphanet; 334; Familial atrial fibrillation.
PharmGKB; PA303; -.
eggNOG; ENOG410II8M; Eukaryota.
eggNOG; ENOG4111M25; LUCA.
GeneTree; ENSGT00900000141020; -.
HOGENOM; HOG000118120; -.
HOVERGEN; HBG003443; -.
InParanoid; O60939; -.
KO; K04846; -.
OMA; HGKIYLQ; -.
OrthoDB; EOG091G0O9E; -.
PhylomeDB; O60939; -.
TreeFam; TF331728; -.
Reactome; R-HSA-445095; Interaction between L1 and Ankyrins.
Reactome; R-HSA-5576892; Phase 0 - rapid depolarisation.
ChiTaRS; SCN2B; human.
GeneWiki; SCN2B; -.
GenomeRNAi; 6327; -.
PMAP-CutDB; O60939; -.
PRO; PR:O60939; -.
Proteomes; UP000005640; Chromosome 11.
Bgee; ENSG00000149575; -.
CleanEx; HS_SCN2B; -.
ExpressionAtlas; O60939; baseline and differential.
Genevisible; O60939; HS.
GO; GO:0001518; C:voltage-gated sodium channel complex; IDA:BHF-UCL.
GO; GO:0017080; F:sodium channel regulator activity; IDA:BHF-UCL.
GO; GO:0005244; F:voltage-gated ion channel activity; IEA:UniProtKB-KW.
GO; GO:0086006; F:voltage-gated sodium channel activity involved in cardiac muscle cell action potential; IMP:BHF-UCL.
GO; GO:0086002; P:cardiac muscle cell action potential involved in contraction; IMP:BHF-UCL.
GO; GO:0060048; P:cardiac muscle contraction; IMP:BHF-UCL.
GO; GO:0007268; P:chemical synaptic transmission; TAS:ProtInc.
GO; GO:0086012; P:membrane depolarization during cardiac muscle cell action potential; IMP:BHF-UCL.
GO; GO:0007399; P:nervous system development; IEA:Ensembl.
GO; GO:0060371; P:regulation of atrial cardiac muscle cell membrane depolarization; IMP:BHF-UCL.
GO; GO:0086091; P:regulation of heart rate by cardiac conduction; IMP:BHF-UCL.
GO; GO:2000649; P:regulation of sodium ion transmembrane transporter activity; IDA:BHF-UCL.
GO; GO:0046684; P:response to pyrethroid; IEA:Ensembl.
GO; GO:0035725; P:sodium ion transmembrane transport; IDA:BHF-UCL.
Gene3D; 2.60.40.10; -; 1.
InterPro; IPR007110; Ig-like_dom.
InterPro; IPR036179; Ig-like_dom_sf.
InterPro; IPR013783; Ig-like_fold.
InterPro; IPR003599; Ig_sub.
InterPro; IPR013106; Ig_V-set.
InterPro; IPR000920; Myelin_P0-rel.
InterPro; IPR029873; SCN2B.
PANTHER; PTHR13869; PTHR13869; 1.
PANTHER; PTHR13869:SF3; PTHR13869:SF3; 1.
Pfam; PF07686; V-set; 1.
PRINTS; PR00213; MYELINP0.
SMART; SM00409; IG; 1.
SUPFAM; SSF48726; SSF48726; 1.
PROSITE; PS50835; IG_LIKE; 1.
1: Evidence at protein level;
3D-structure; Atrial fibrillation; Brugada syndrome;
Complete proteome; Disease mutation; Disulfide bond; Glycoprotein;
Immunoglobulin domain; Ion channel; Ion transport; Membrane;
Phosphoprotein; Polymorphism; Reference proteome; Signal; Sodium;
Sodium channel; Sodium transport; Transmembrane; Transmembrane helix;
Transport; Voltage-gated channel.
SIGNAL 1 29 {ECO:0000250}.
CHAIN 30 215 Sodium channel subunit beta-2.
/FTId=PRO_0000014931.
TOPO_DOM 30 159 Extracellular. {ECO:0000255}.
TRANSMEM 160 180 Helical. {ECO:0000255}.
TOPO_DOM 181 215 Cytoplasmic. {ECO:0000255}.
DOMAIN 32 154 Ig-like C2-type.
MOD_RES 192 192 Phosphoserine.
{ECO:0000250|UniProtKB:P54900}.
MOD_RES 204 204 Phosphothreonine.
{ECO:0000250|UniProtKB:P54900}.
CARBOHYD 42 42 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 66 66 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 74 74 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
DISULFID 50 127 {ECO:0000255|PROSITE-ProRule:PRU00114,
ECO:0000269|PubMed:22992729}.
DISULFID 55 55 Interchain; with alpha subunit.
{ECO:0000255|PROSITE-ProRule:PRU00114,
ECO:0000269|PubMed:22992729}.
VARIANT 28 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).
{ECO:0000269|PubMed:19808477}.
/FTId=VAR_070229.
VARIANT 28 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).
{ECO:0000269|PubMed:19808477}.
/FTId=VAR_029131.
VARIANT 47 47 R -> H (in dbSNP:rs17121818).
/FTId=VAR_029132.
VARIANT 211 211 D -> 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; dbSNP:rs587777023).
{ECO:0000269|PubMed:23559163}.
/FTId=VAR_070230.
CONFLICT 2 2 H -> Q (in Ref. 1; AAC26013).
{ECO:0000305}.
CONFLICT 8 8 P -> L (in Ref. 1; AAC26013).
{ECO:0000305}.
CONFLICT 15 15 T -> N (in Ref. 1; AAC26013).
{ECO:0000305}.
CONFLICT 48 48 L -> Q (in Ref. 1; AAC26013).
{ECO:0000305}.
CONFLICT 68 68 T -> S (in Ref. 1; AAC26013).
{ECO:0000305}.
CONFLICT 156 156 S -> F (in Ref. 3; AAD47196).
{ECO:0000305}.
CONFLICT 178 179 MV -> TA (in Ref. 1; AAC26013).
{ECO:0000305}.
STRAND 36 41 {ECO:0000244|PDB:5FEB}.
STRAND 46 48 {ECO:0000244|PDB:5FEB}.
TURN 60 62 {ECO:0000244|PDB:5FEB}.
STRAND 64 72 {ECO:0000244|PDB:5FEB}.
STRAND 77 89 {ECO:0000244|PDB:5FEB}.
HELIX 93 95 {ECO:0000244|PDB:5FEB}.
STRAND 99 101 {ECO:0000244|PDB:5FEB}.
HELIX 105 107 {ECO:0000244|PDB:5FEB}.
STRAND 112 114 {ECO:0000244|PDB:5FEB}.
HELIX 119 121 {ECO:0000244|PDB:5FEB}.
STRAND 123 130 {ECO:0000244|PDB:5FEB}.
STRAND 138 147 {ECO:0000244|PDB:5FEB}.
SEQUENCE 215 AA; 24326 MW; 94A30A60A32683F3 CRC64;
MHRDAWLPRP AFSLTGLSLF FSLVPPGRSM EVTVPATLNV LNGSDARLPC TFNSCYTVNH
KQFSLNWTYQ ECNNCSEEMF LQFRMKIINL KLERFQDRVE FSGNPSKYDV SVMLRNVQPE
DEGIYNCYIM NPPDRHRGHG KIHLQVLMEE PPERDSTVAV IVGASVGGFL AVVILVLMVV
KCVRRKKEQK LSTDDLKTEE EGKTDGEGNP DDGAK


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