Q8IWT1 (SCN4B_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Sodium channel subunit beta-4

Gene names

Name:

SCN4B

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	228 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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 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. Associates with SCN2A By similarity.
Subcellular location	Membrane; Single-pass type I membrane protein Probable.
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 a number of interchain disulfide bonds with SCN2A By similarity.
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.3
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.
Sequence caution	The sequence AAH35017.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Ion transport Sodium transport Transport
Cellular component	Membrane
Coding sequence diversity	Alternative splicing
Disease	Disease mutation Long QT syndrome
Domain	Immunoglobulin domain Signal Transmembrane Transmembrane helix
Ligand	Sodium
Molecular function	Ion channel Sodium channel Voltage-gated channel
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	AV node cell to bundle of His cell communication Inferred from mutant phenotype Ref.3. Source: BHF-UCL cardiac muscle contraction Inferred from mutant phenotype Ref.3. Source: BHF-UCL positive regulation of sodium ion transport Inferred from direct assay Ref.3. Source: BHF-UCL regulation of cardiac muscle cell action potential involved in contraction Inferred from mutant phenotype Ref.3. Source: BHF-UCL regulation of heart rate by cardiac conduction Inferred from mutant phenotype Ref.3. Source: BHF-UCL regulation of sodium ion transmembrane transporter activity Inferred from direct assay Ref.3. Source: BHF-UCL regulation of ventricular cardiac muscle cell membrane repolarization Inferred from mutant phenotype Ref.3. Source: BHF-UCL
Cellular_component	intercalated disc Inferred from sequence or structural similarity. Source: BHF-UCL voltage-gated sodium channel complex Inferred from direct assay Ref.1. Source: UniProtKB
Molecular_function	sodium channel regulator activity Inferred from direct assay Ref.3. Source: BHF-UCL voltage-gated sodium channel activity involved in regulation of cardiac muscle cell action potential Inferred from mutant phenotype Ref.3. Source: BHF-UCL
Complete GO annotation...

Alternative products

This entry describes 2 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:
     1-20: MPGAGDGGKAPARWLGTGLL → ASPSRAPGWWGFIKGGGAPYT

Note: Incomplete sequence. No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 30	30	Potential
	Chain	31 – 228	198	Sodium channel subunit beta-4		PRO_0000014937
Regions
	Topological domain	31 – 162	132	Extracellular Potential
	Transmembrane	163 – 183	21	Helical; Potential
	Topological domain	184 – 228	45	Cytoplasmic Potential
	Domain	31 – 148	118	Ig-like C2-type
Amino acid modifications
	Glycosylation	45	1	N-linked (GlcNAc...) Potential
	Glycosylation	71	1	N-linked (GlcNAc...) Potential
	Glycosylation	113	1	N-linked (GlcNAc...) Potential
	Disulfide bond	53 ↔ 131		By similarity
	Disulfide bond	58		Interchain; with alpha subunit By similarity
Natural variations
	Alternative sequence	1 – 20	20	MPGAG…GTGLL → ASPSRAPGWWGFIKGGGAPY T in isoform 2.		VSP_012378
	Natural variant	179	1	L → F in LQT10; increase in late sodium current. Ref.3		VAR_043488
Experimental info
	Sequence conflict	40	1	D → Y Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified March 1, 2003. Version 1. Checksum: 2F17E1210E8EFEF8	FASTA	228	24,969
	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
	Isoform 2 [UniParc]. Checksum: 7F4A88E93918943D	FASTA	229	25,207
	10 20 30 40 50 60 ASPSRAPGWW GFIKGGGAPY TGLFLLPVTL SLEVSVGKAT DIYAVNGTEI LLPCTFSSCF 70 80 90 100 110 120 GFEDLHFRWT YNSSDAFKIL IEGTVKNEKS DPKVTLKDDD RITLVGSTKE KMNNISIVLR 130 140 150 160 170 180 DLEFSDTGKY TCHVKNPKEN NLQHHATIFL QVVDRLEEVD NTVTLIILAV VGGVIGLLIL 190 200 210 220 ILLIKKLIIF ILKKTREKKK ECLVSSSGND NTENGLPGSK AEEKPPSKV

References

	« Hide 'large scale' referencesShow '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]	"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.
[3]	"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. BC035017 mRNA. Translation: AAH35017.1. Different initiation.
IPI	IPI00217376. IPI00514804.
RefSeq	NP_001135820.1. NM_001142348.1. NP_001135821.1. NM_001142349.1. NP_777594.1. NM_174934.3.
UniGene	Hs.65239.
3D structure databases
ProteinModelPortal	Q8IWT1.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000322460.
Protein family/group databases
TCDB	8.A.17.2.2. Na+ channel auxiliary subunit beta1-beta4 (SCA-beta) family.
PTM databases
PhosphoSite	Q8IWT1.
Polymorphism databases
DMDM	57012701.
Proteomic databases
PaxDb	Q8IWT1.
PRIDE	Q8IWT1.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000324727; ENSP00000322460; ENSG00000177098.
GeneID	6330.
KEGG	hsa:6330.
UCSC	uc001pse.3. human.
Organism-specific databases
CTD	6330.
GeneCards	GC11M118004.
HGNC	HGNC:10592. SCN4B.
HPA	HPA017293.
MIM	608256. gene. 611819. phenotype.
neXtProt	NX_Q8IWT1.
Orphanet	101016. Romano-Ward syndrome.
PharmGKB	PA35007.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG46712.
HOGENOM	HOG000048715.
HOVERGEN	HBG056581.
InParanoid	Q8IWT1.
KO	K04848.
OMA	REKKKEC.
PhylomeDB	Q8IWT1.
Gene expression databases
ArrayExpress	Q8IWT1.
Bgee	Q8IWT1.
CleanEx	HS_SCN4B.
Genevestigator	Q8IWT1.
GermOnline	ENSG00000177098. Homo sapiens.
Family and domain databases
Gene3D	2.60.40.10. 1 hit.
InterPro	IPR007110. Ig-like_dom. IPR013783. Ig-like_fold. IPR003599. Ig_sub. IPR013106. Ig_V-set. [Graphical view]
Pfam	PF07686. V-set. 1 hit. [Graphical view]
SMART	SM00409. IG. 1 hit. [Graphical view]
PROSITE	PS50835. IG_LIKE. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	Q8IWT1.
ChEMBL	CHEMBL4689.
GenomeRNAi	6330.
NextBio	24574.
PMAP-CutDB	Q8IWT1.
SOURCE	Search...

Entry information

Entry name

SCN4B_HUMAN

Accession

Primary (citable) accession number: Q8IWT1
Secondary accession number(s): Q6PIG5

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 4, 2005
Last sequence update:	March 1, 2003
Last modified:	May 1, 2013
This is version 91 of the entry and version 1 of the sequence. [Complete history]

Entry status

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.