SCN1B_HUMAN
ID SCN1B_HUMAN Reviewed; 218 AA.
AC Q07699; Q5TZZ4; Q6TN97;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 202.
DE RecName: Full=Sodium channel subunit beta-1;
DE Flags: Precursor;
GN Name=SCN1B;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, AND TISSUE SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=8394762; DOI=10.1093/hmg/2.6.745;
RA McClatchey A.I., Cannon S.C., Slaugenhaupt S.A., Gusella J.F.;
RT "The cloning and expression of a sodium channel beta 1-subunit cDNA from
RT human brain.";
RL Hum. Mol. Genet. 2:745-749(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION, AND
RP TISSUE SPECIFICITY.
RC TISSUE=Heart, and Skeletal muscle;
RX PubMed=8125980; DOI=10.1016/s0021-9258(17)37325-8;
RA Makita N., Bennett P.B. Jr., George A.L. Jr.;
RT "Voltage-gated Na+ channel beta 1 subunit mRNA expressed in adult human
RT skeletal muscle, heart, and brain is encoded by a single gene.";
RL J. Biol. Chem. 269:7571-7578(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Placenta;
RX PubMed=7851891; DOI=10.1006/geno.1994.1551;
RA Makita N., Sloan-Brown K., Weghuis D.O., Ropers H.-H., George A.L. Jr.;
RT "Genomic organization and chromosomal assignment of the human voltage-gated
RT Na+ channel beta 1 subunit gene (SCN1B).";
RL Genomics 23:628-634(1994).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION (ISOFORMS 1 AND 2),
RP SUBCELLULAR LOCATION (ISOFORM 2), AND TISSUE SPECIFICITY.
RX PubMed=14622265; DOI=10.1046/j.1432-1033.2003.03878.x;
RA Qin N., D'Andrea M.R., Lubin M.L., Shafaee N., Codd E.E., Correa A.M.;
RT "Molecular cloning and functional expression of the human sodium channel
RT beta1B subunit, a novel splicing variant of the beta1 subunit.";
RL Eur. J. Biochem. 270:4762-4770(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Skeletal muscle;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG NHLBI resequencing and genotyping service (RS&G);
RL Submitted (JUN-2006) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [10]
RP INTERACTION WITH SCN1A, AND FUNCTION.
RX PubMed=15525788; DOI=10.1523/jneurosci.2034-04.2004;
RA Spampanato J., Kearney J.A., de Haan G., McEwen D.P., Escayg A., Aradi I.,
RA MacDonald B.T., Levin S.I., Soltesz I., Benna P., Montalenti E., Isom L.L.,
RA Goldin A.L., Meisler M.H.;
RT "A novel epilepsy mutation in the sodium channel SCN1A identifies a
RT cytoplasmic domain for beta subunit interaction.";
RL J. Neurosci. 24:10022-10034(2004).
RN [11]
RP INVOLVEMENT IN BRGDA5, VARIANT GLN-87, AND FUNCTION.
RX PubMed=18464934; DOI=10.1172/jci33891;
RA Watanabe H., Koopmann T.T., Le Scouarnec S., Yang T., Ingram C.R.,
RA Schott J.J., Demolombe S., Probst V., Anselme F., Escande D.,
RA Wiesfeld A.C., Pfeufer A., Kaab S., Wichmann H.E., Hasdemir C., Aizawa Y.,
RA Wilde A.A., Roden D.M., Bezzina C.R.;
RT "Sodium channel beta1 subunit mutations associated with Brugada syndrome
RT and cardiac conduction disease in humans.";
RL J. Clin. Invest. 118:2260-2268(2008).
RN [12]
RP FUNCTION, SUBCELLULAR LOCATION, INVOLVEMENT IN DEE52, VARIANT DEE52
RP CYS-125, AND CHARACTERIZATION OF VARIANT DEE52 CYS-125.
RX PubMed=19710327; DOI=10.1523/jneurosci.2475-09.2009;
RA Patino G.A., Claes L.R., Lopez-Santiago L.F., Slat E.A., Dondeti R.S.,
RA Chen C., O'Malley H.A., Gray C.B., Miyazaki H., Nukina N., Oyama F.,
RA De Jonghe P., Isom L.L.;
RT "A functional null mutation of SCN1B in a patient with Dravet syndrome.";
RL J. Neurosci. 29:10764-10778(2009).
RN [13]
RP FUNCTION (ISOFORM 2), SUBCELLULAR LOCATION (ISOFORMS 1 AND 2), AND
RP INTERACTION WITH SCN1A; SCN3A AND SCN5A (ISOFORM 1).
RX PubMed=21994374; DOI=10.1523/jneurosci.0361-11.2011;
RA Patino G.A., Brackenbury W.J., Bao Y., Lopez-Santiago L.F., O'Malley H.A.,
RA Chen C., Calhoun J.D., Lafreniere R.G., Cossette P., Rouleau G.A.,
RA Isom L.L.;
RT "Voltage-gated Na+ channel beta1B: a secreted cell adhesion molecule
RT involved in human epilepsy.";
RL J. Neurosci. 31:14577-14591(2011).
RN [14]
RP INTERACTION WITH SCN8A.
RX PubMed=26900580; DOI=10.1002/acn3.276;
RA Wagnon J.L., Barker B.S., Hounshell J.A., Haaxma C.A., Shealy A., Moss T.,
RA Parikh S., Messer R.D., Patel M.K., Meisler M.H.;
RT "Pathogenic mechanism of recurrent mutations of SCN8A in epileptic
RT encephalopathy.";
RL Ann. Clin. Transl. Neurol. 3:114-123(2016).
RN [15]
RP FUNCTION, SUBCELLULAR LOCATION, AND CHARACTERIZATION OF VARIANT ASN-25.
RX PubMed=29992740; DOI=10.1002/humu.23589;
RA Baroni D., Picco C., Moran O.;
RT "A mutation of SCN1B associated with GEFS+ causes functional and maturation
RT defects of the voltage-dependent sodium channel.";
RL Hum. Mutat. 39:1402-1415(2018).
RN [16] {ECO:0007744|PDB:6AGF}
RP STRUCTURE BY ELECTRON MICROSCOPY (3.20 ANGSTROMS) IN COMPLEX WITH SCN4A,
RP SUBCELLULAR LOCATION, TOPOLOGY, GLYCOSYLATION AT ASN-110 AND ASN-114, AND
RP DISULFIDE BONDS.
RX PubMed=30190309; DOI=10.1126/science.aau2486;
RA Pan X., Li Z., Zhou Q., Shen H., Wu K., Huang X., Chen J., Zhang J.,
RA Zhu X., Lei J., Xiong W., Gong H., Xiao B., Yan N.;
RT "Structure of the human voltage-gated sodium channel Nav1.4 in complex with
RT beta1.";
RL Science 362:0-0(2018).
RN [17]
RP STRUCTURE BY ELECTRON MICROSCOPY (3.2 ANGSTROMS) IN COMPLEX WITH SCN9A;
RP SCN2B; PROTOTOXIN-II; TETRODOTOXIN; HUWENTOXIN-IV AND SAXITOXIN,
RP GLYCOSYLATION AT ASN-93; ASN-110; ASN-114 AND ASN-135, AND DISULFIDE BOND.
RX PubMed=30765606; DOI=10.1126/science.aaw2493;
RA Shen H., Liu D., Wu K., Lei J., Yan N.;
RT "Structures of human Nav1.7 channel in complex with auxiliary subunits and
RT animal toxins.";
RL Science 363:1303-1308(2019).
RN [18]
RP VARIANT GEFS+1 TRP-121.
RX PubMed=9697698; DOI=10.1038/1252;
RA Wallace R.H., Wang D.W., Singh R., Scheffer I.E., George A.L. Jr.,
RA Phillips H.A., Saar K., Reis A., Johnson E.W., Sutherland G.R.,
RA Berkovic S.F., Mulley J.C.;
RT "Febrile seizures and generalized epilepsy associated with a mutation in
RT the Na(+)-channel beta-1 subunit gene SCN1B.";
RL Nat. Genet. 19:366-370(1998).
RN [19]
RP CHARACTERIZATION OF VARIANT GEFS+1 TRP-121, INTERACTION WITH SCN1A, AND
RP SUBCELLULAR LOCATION.
RX PubMed=17928445; DOI=10.1523/jneurosci.3515-07.2007;
RA Rusconi R., Scalmani P., Cassulini R.R., Giunti G., Gambardella A.,
RA Franceschetti S., Annesi G., Wanke E., Mantegazza M.;
RT "Modulatory proteins can rescue a trafficking defective epileptogenic
RT Nav1.1 Na+ channel mutant.";
RL J. Neurosci. 27:11037-11046(2007).
RN [20]
RP VARIANTS ATFB13 HIS-85 AND ASN-153, AND CHARACTERIZATION OF VARIANTS ATFB13
RP HIS-85 AND ASN-153.
RX PubMed=19808477; DOI=10.1161/circep.108.779181;
RA Watanabe H., Darbar D., Kaiser D.W., Jiramongkolchai K., Chopra S.,
RA Donahue B.S., Kannankeril P.J., Roden D.M.;
RT "Mutations in sodium channel beta1- and beta2-subunits associated with
RT atrial fibrillation.";
RL Circ. Arrhythm. Electrophysiol. 2:268-275(2009).
RN [21]
RP VARIANTS ASN-25; ILE-138; ILE-208; TYR-211 AND ASP-213.
RX PubMed=19522081; DOI=10.1111/j.1399-0004.2009.01155.x;
RA Orrico A., Galli L., Grosso S., Buoni S., Pianigiani R., Balestri P.,
RA Sorrentino V.;
RT "Mutational analysis of the SCN1A, SCN1B and GABRG2 genes in 150 Italian
RT patients with idiopathic childhood epilepsies.";
RL Clin. Genet. 75:579-581(2009).
RN [22]
RP VARIANT GEFS+1 LEU-125.
RX PubMed=21040232; DOI=10.1111/j.1468-1331.2010.03216.x;
RA Fendri-Kriaa N., Kammoun F., Salem I.H., Kifagi C., Mkaouar-Rebai E.,
RA Hsairi I., Rebai A., Triki C., Fakhfakh F.;
RT "New mutation c.374C>T and a putative disease-associated haplotype within
RT SCN1B gene in Tunisian families with febrile seizures.";
RL Eur. J. Neurol. 18:695-702(2011).
RN [23]
RP VARIANT DEE52 THR-106.
RX PubMed=23148524; DOI=10.1111/epi.12040;
RA Ogiwara I., Nakayama T., Yamagata T., Ohtani H., Mazaki E., Tsuchiya S.,
RA Inoue Y., Yamakawa K.;
RT "A homozygous mutation of voltage-gated sodium channel beta(I) gene SCN1B
RT in a patient with Dravet syndrome.";
RL Epilepsia 53:E200-E203(2012).
CC -!- FUNCTION: Regulatory subunit of multiple voltage-gated sodium channel
CC complexes that play important roles in excitable membranes in brain,
CC heart and skeletal muscle. Enhances the presence of the pore-forming
CC alpha subunit at the cell surface and modulates channel gating
CC characteristics and the rate of channel inactivation. Modulates the
CC activity of multiple pore-forming alpha subunits, such as SCN1A, SCN2A,
CC SCN3A, SCN4A, SCN5A and SCN10A. {ECO:0000269|PubMed:14622265,
CC ECO:0000269|PubMed:15525788, ECO:0000269|PubMed:18464934,
CC ECO:0000269|PubMed:19710327, ECO:0000269|PubMed:21994374,
CC ECO:0000269|PubMed:29992740, ECO:0000269|PubMed:8125980,
CC ECO:0000269|PubMed:8394762}.
CC -!- FUNCTION: [Isoform 2]: Cell adhesion molecule that plays a critical
CC role in neuronal migration and pathfinding during brain development.
CC Stimulates neurite outgrowth (PubMed:21994374). Has no regulatory
CC function on the SCN2A sodium channel complex (PubMed:14622265).
CC {ECO:0000269|PubMed:14622265, ECO:0000269|PubMed:21994374}.
CC -!- SUBUNIT: Component of a voltage-sensitive sodium channel complex that
CC consists of a pore-forming alpha subunit and one or more regulatory
CC beta subunits (PubMed:15525788, PubMed:21994374, PubMed:30190309).
CC Interacts with SCN4A (PubMed:8125980). Interacts with NFASC. Interacts
CC with SCN10A (By similarity). Interacts with SCN1A (PubMed:15525788,
CC PubMed:21994374, PubMed:17928445). Interacts with SCN3A
CC (PubMed:21994374). Interacts with SCN5A (PubMed:21994374). Interacts
CC with SCN8A (PubMed:26900580). {ECO:0000250|UniProtKB:Q00954,
CC ECO:0000269|PubMed:15525788, ECO:0000269|PubMed:17928445,
CC ECO:0000269|PubMed:21994374, ECO:0000269|PubMed:26900580,
CC ECO:0000269|PubMed:30190309, ECO:0000269|PubMed:8125980}.
CC -!- INTERACTION:
CC Q07699-1; P35499: SCN4A; NbExp=2; IntAct=EBI-20974499, EBI-16813249;
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cell membrane
CC {ECO:0000269|PubMed:17928445, ECO:0000269|PubMed:19710327,
CC ECO:0000269|PubMed:21994374, ECO:0000269|PubMed:29992740,
CC ECO:0000269|PubMed:30190309, ECO:0000305|PubMed:8125980}; Single-pass
CC type I membrane protein {ECO:0000269|PubMed:30190309,
CC ECO:0000305|PubMed:8125980}. Perikaryon {ECO:0000250|UniProtKB:P97952}.
CC Cell projection {ECO:0000250|UniProtKB:P97952}. Cell projection, axon
CC {ECO:0000250|UniProtKB:Q00954}. Note=Detected at nodes of Ranvier on
CC the sciatic nerve. {ECO:0000250|UniProtKB:Q00954}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Perikaryon
CC {ECO:0000269|PubMed:14622265}. Cell projection
CC {ECO:0000269|PubMed:14622265}. Secreted {ECO:0000269|PubMed:21994374}.
CC Note=Detected on Purkinje cells and their cell projections and on
CC neuronal cell projections. {ECO:0000269|PubMed:14622265}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=Beta-1;
CC IsoId=Q07699-1; Sequence=Displayed;
CC Name=2; Synonyms=Beta-1B, beta1A, beta1B;
CC IsoId=Q07699-2; Sequence=VSP_041982;
CC -!- TISSUE SPECIFICITY: The overall expression of isoform 1 and isoform 2
CC is very similar. Isoform 1 is abundantly expressed in skeletal muscle,
CC heart and brain. Isoform 2 is highly expressed in brain and skeletal
CC muscle and present at a very low level in heart, placenta, lung, liver,
CC kidney and pancreas. In brain, isoform 2 is most abundant in the
CC cerebellum, followed by the cerebral cortex and occipital lobe, while
CC isoform 1 levels are higher in the cortex compared to the cerebellum.
CC Isoform 2 is expressed in many regions of the brain, including
CC cerebellar Purkinje cells, cortex pyramidal neurons and many of the
CC neuronal fibers throughout the brain (at protein level). Also detected
CC in dorsal root ganglion, in fibers of the spinal nerve and in cortical
CC neurons and their processes (at protein level).
CC {ECO:0000269|PubMed:14622265, ECO:0000269|PubMed:8125980,
CC ECO:0000269|PubMed:8394762}.
CC -!- DISEASE: Generalized epilepsy with febrile seizures plus 1 (GEFS+1)
CC [MIM:604233]: A rare autosomal dominant, familial condition with
CC incomplete penetrance and large intrafamilial variability. Patients
CC display febrile seizures persisting sometimes beyond the age of 6 years
CC and/or a variety of afebrile seizure types. This disease combines
CC febrile seizures, generalized seizures often precipitated by fever at
CC age 6 years or more, and partial seizures, with a variable degree of
CC severity. {ECO:0000269|PubMed:17928445, ECO:0000269|PubMed:21040232,
CC ECO:0000269|PubMed:9697698}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Brugada syndrome 5 (BRGDA5) [MIM:612838]: A tachyarrhythmia
CC characterized by right bundle branch block and ST segment elevation on
CC an electrocardiogram (ECG). It can cause the ventricles to beat so fast
CC that the blood is prevented from circulating efficiently in the body.
CC When this situation occurs, the individual will faint and may die in a
CC few minutes if the heart is not reset. {ECO:0000269|PubMed:18464934}.
CC Note=The gene represented in this entry may be involved in disease
CC pathogenesis.
CC -!- DISEASE: Atrial fibrillation, familial, 13 (ATFB13) [MIM:615377]: A
CC familial form of atrial fibrillation, a common sustained cardiac rhythm
CC disturbance. Atrial fibrillation is characterized by disorganized
CC atrial electrical activity and ineffective atrial contraction promoting
CC blood stasis in the atria and reduces ventricular filling. It can
CC result in palpitations, syncope, thromboembolic stroke, and congestive
CC heart failure. {ECO:0000269|PubMed:19808477}. Note=The disease is
CC caused by variants affecting the gene represented in this entry.
CC -!- DISEASE: Developmental and epileptic encephalopathy 52 (DEE52)
CC [MIM:617350]: A form of epileptic encephalopathy, a heterogeneous group
CC of severe early-onset epilepsies characterized by refractory seizures,
CC neurodevelopmental impairment, and poor prognosis. Development is
CC normal prior to seizure onset, after which cognitive and motor delays
CC become apparent. DEE52 inheritance is autosomal recessive.
CC {ECO:0000269|PubMed:19710327, ECO:0000269|PubMed:23148524}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- MISCELLANEOUS: [Isoform 2]: Due to intron 3 retention. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the sodium channel auxiliary subunit SCN1B (TC
CC 8.A.17) family. {ECO:0000305}.
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DR EMBL; L10338; AAA60391.1; -; mRNA.
DR EMBL; L16242; AAA61277.1; -; mRNA.
DR EMBL; U12193; AAB97608.1; -; Genomic_DNA.
DR EMBL; U12189; AAB97608.1; JOINED; Genomic_DNA.
DR EMBL; U12190; AAB97608.1; JOINED; Genomic_DNA.
DR EMBL; U12191; AAB97608.1; JOINED; Genomic_DNA.
DR EMBL; U12192; AAB97608.1; JOINED; Genomic_DNA.
DR EMBL; AY391842; AAR25552.1; -; mRNA.
DR EMBL; AK313279; BAG36087.1; -; mRNA.
DR EMBL; DQ677665; ABQ01236.1; -; Genomic_DNA.
DR EMBL; BT019923; AAV38726.1; -; mRNA.
DR EMBL; AC020907; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC067122; AAH67122.1; -; mRNA.
DR CCDS; CCDS12441.1; -. [Q07699-1]
DR CCDS; CCDS46047.1; -. [Q07699-2]
DR PIR; A55734; A55734.
DR RefSeq; NP_001028.1; NM_001037.4. [Q07699-1]
DR RefSeq; NP_001308534.1; NM_001321605.1.
DR RefSeq; NP_950238.1; NM_199037.4. [Q07699-2]
DR PDB; 6AGF; EM; 3.20 A; B=1-218.
DR PDB; 6J8G; EM; 3.20 A; B=1-218.
DR PDB; 6J8H; EM; 3.20 A; B=1-218.
DR PDB; 6J8I; EM; 3.20 A; B=1-218.
DR PDB; 6J8J; EM; 3.20 A; B=1-218.
DR PDB; 7W77; EM; 3.30 A; B=1-218.
DR PDB; 7W7F; EM; 3.35 A; B=1-218.
DR PDBsum; 6AGF; -.
DR PDBsum; 6J8G; -.
DR PDBsum; 6J8H; -.
DR PDBsum; 6J8I; -.
DR PDBsum; 6J8J; -.
DR PDBsum; 7W77; -.
DR PDBsum; 7W7F; -.
DR AlphaFoldDB; Q07699; -.
DR SMR; Q07699; -.
DR BioGRID; 112229; 16.
DR IntAct; Q07699; 4.
DR MINT; Q07699; -.
DR STRING; 9606.ENSP00000396915; -.
DR BindingDB; Q07699; -.
DR ChEMBL; CHEMBL4523668; -.
DR ChEMBL; CHEMBL4523669; -.
DR ChEMBL; CHEMBL4523670; -.
DR ChEMBL; CHEMBL4523671; -.
DR ChEMBL; CHEMBL4523672; -.
DR ChEMBL; CHEMBL4630760; -.
DR ChEMBL; CHEMBL4630762; -.
DR ChEMBL; CHEMBL4630763; -.
DR ChEMBL; CHEMBL4630765; -.
DR DrugBank; DB05541; Brivaracetam.
DR DrugBank; DB00907; Cocaine.
DR DrugBank; DB13269; Dichlorobenzyl alcohol.
DR DrugBank; DB13961; Fish oil.
DR DrugBank; DB00776; Oxcarbazepine.
DR DrugBank; DB00252; Phenytoin.
DR DrugBank; DB00243; Ranolazine.
DR DrugBank; DB00313; Valproic acid.
DR DrugBank; DB00909; Zonisamide.
DR DrugCentral; Q07699; -.
DR GlyGen; Q07699; 4 sites.
DR iPTMnet; Q07699; -.
DR PhosphoSitePlus; Q07699; -.
DR BioMuta; SCN1B; -.
DR DMDM; 1705868; -.
DR MassIVE; Q07699; -.
DR PaxDb; Q07699; -.
DR PeptideAtlas; Q07699; -.
DR PRIDE; Q07699; -.
DR ProteomicsDB; 58527; -. [Q07699-1]
DR ProteomicsDB; 58528; -. [Q07699-2]
DR Antibodypedia; 29258; 220 antibodies from 29 providers.
DR DNASU; 6324; -.
DR Ensembl; ENST00000262631.11; ENSP00000262631.3; ENSG00000105711.14. [Q07699-1]
DR Ensembl; ENST00000415950.5; ENSP00000396915.2; ENSG00000105711.14. [Q07699-2]
DR Ensembl; ENST00000638536.1; ENSP00000492022.1; ENSG00000105711.14. [Q07699-1]
DR GeneID; 6324; -.
DR KEGG; hsa:6324; -.
DR MANE-Select; ENST00000262631.11; ENSP00000262631.3; NM_001037.5; NP_001028.1.
DR UCSC; uc002nxo.3; human. [Q07699-1]
DR CTD; 6324; -.
DR DisGeNET; 6324; -.
DR GeneCards; SCN1B; -.
DR GeneReviews; SCN1B; -.
DR HGNC; HGNC:10586; SCN1B.
DR HPA; ENSG00000105711; Group enriched (brain, skeletal muscle, tongue).
DR MalaCards; SCN1B; -.
DR MIM; 600235; gene.
DR MIM; 604233; phenotype.
DR MIM; 612838; phenotype.
DR MIM; 615377; phenotype.
DR MIM; 617350; phenotype.
DR neXtProt; NX_Q07699; -.
DR OpenTargets; ENSG00000105711; -.
DR Orphanet; 130; Brugada syndrome.
DR Orphanet; 33069; Dravet syndrome.
DR Orphanet; 1934; Early infantile epileptic encephalopathy.
DR Orphanet; 334; Familial atrial fibrillation.
DR Orphanet; 871; Familial progressive cardiac conduction defect.
DR Orphanet; 36387; Generalized epilepsy with febrile seizures-plus.
DR PharmGKB; PA302; -.
DR VEuPathDB; HostDB:ENSG00000105711; -.
DR eggNOG; ENOG502R0UM; Eukaryota.
DR GeneTree; ENSGT00390000018560; -.
DR HOGENOM; CLU_096296_0_0_1; -.
DR InParanoid; Q07699; -.
DR OMA; DRIDWNG; -.
DR OrthoDB; 1041959at2759; -.
DR PhylomeDB; Q07699; -.
DR TreeFam; TF332097; -.
DR PathwayCommons; Q07699; -.
DR Reactome; R-HSA-445095; Interaction between L1 and Ankyrins.
DR Reactome; R-HSA-5576892; Phase 0 - rapid depolarisation.
DR Reactome; R-HSA-9717207; Sensory perception of sweet, bitter, and umami (glutamate) taste.
DR SignaLink; Q07699; -.
DR BioGRID-ORCS; 6324; 14 hits in 1076 CRISPR screens.
DR GeneWiki; SCN1B; -.
DR GenomeRNAi; 6324; -.
DR Pharos; Q07699; Tbio.
DR PRO; PR:Q07699; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q07699; protein.
DR Bgee; ENSG00000105711; Expressed in primary visual cortex and 95 other tissues.
DR ExpressionAtlas; Q07699; baseline and differential.
DR Genevisible; Q07699; HS.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0014704; C:intercalated disc; ISS:BHF-UCL.
DR GO; GO:0033268; C:node of Ranvier; ISS:BHF-UCL.
DR GO; GO:0043204; C:perikaryon; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0030315; C:T-tubule; ISS:BHF-UCL.
DR GO; GO:0001518; C:voltage-gated sodium channel complex; IDA:UniProtKB.
DR GO; GO:0019871; F:sodium channel inhibitor activity; ISS:BHF-UCL.
DR GO; GO:0017080; F:sodium channel regulator activity; IDA:UniProtKB.
DR GO; GO:0044325; F:transmembrane transporter binding; IBA:GO_Central.
DR GO; GO:0005244; F:voltage-gated ion channel activity; IEA:UniProtKB-KW.
DR GO; GO:0005248; F:voltage-gated sodium channel activity; IDA:BHF-UCL.
DR GO; GO:0086006; F:voltage-gated sodium channel activity involved in cardiac muscle cell action potential; IMP:BHF-UCL.
DR GO; GO:0086062; F:voltage-gated sodium channel activity involved in Purkinje myocyte action potential; IMP:BHF-UCL.
DR GO; GO:0007411; P:axon guidance; ISS:BHF-UCL.
DR GO; GO:0061337; P:cardiac conduction; ISS:BHF-UCL.
DR GO; GO:0086002; P:cardiac muscle cell action potential involved in contraction; IMP:BHF-UCL.
DR GO; GO:0060048; P:cardiac muscle contraction; IMP:BHF-UCL.
DR GO; GO:0007155; P:cell adhesion; IEA:UniProtKB-KW.
DR GO; GO:0021966; P:corticospinal neuron axon guidance; ISS:BHF-UCL.
DR GO; GO:0040011; P:locomotion; ISS:BHF-UCL.
DR GO; GO:0051899; P:membrane depolarization; IDA:BHF-UCL.
DR GO; GO:0086012; P:membrane depolarization during cardiac muscle cell action potential; ISS:BHF-UCL.
DR GO; GO:0086047; P:membrane depolarization during Purkinje myocyte cell action potential; IMP:BHF-UCL.
DR GO; GO:0019227; P:neuronal action potential propagation; ISS:BHF-UCL.
DR GO; GO:0010976; P:positive regulation of neuron projection development; ISS:BHF-UCL.
DR GO; GO:0010765; P:positive regulation of sodium ion transport; IDA:BHF-UCL.
DR GO; GO:0060371; P:regulation of atrial cardiac muscle cell membrane depolarization; IMP:BHF-UCL.
DR GO; GO:0086091; P:regulation of heart rate by cardiac conduction; IMP:BHF-UCL.
DR GO; GO:2000649; P:regulation of sodium ion transmembrane transporter activity; IDA:BHF-UCL.
DR GO; GO:0060307; P:regulation of ventricular cardiac muscle cell membrane repolarization; ISS:BHF-UCL.
DR GO; GO:0035725; P:sodium ion transmembrane transport; IDA:BHF-UCL.
DR Gene3D; 2.60.40.10; -; 1.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR013106; Ig_V-set.
DR InterPro; IPR027098; Na_channel_b1/b3.
DR InterPro; IPR044568; Na_chnl_b1.
DR PANTHER; PTHR10546; PTHR10546; 1.
DR PANTHER; PTHR10546:SF2; PTHR10546:SF2; 1.
DR Pfam; PF07686; V-set; 1.
DR SUPFAM; SSF48726; SSF48726; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Atrial fibrillation; Brugada syndrome;
KW Cell adhesion; Cell membrane; Cell projection; Disease variant;
KW Disulfide bond; Epilepsy; Glycoprotein; Immunoglobulin domain; Ion channel;
KW Ion transport; Membrane; Reference proteome; Secreted; Signal; Sodium;
KW Sodium channel; Sodium transport; Transmembrane; Transmembrane helix;
KW Transport; Voltage-gated channel.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT CHAIN 19..218
FT /note="Sodium channel subunit beta-1"
FT /id="PRO_0000014926"
FT TOPO_DOM 19..160
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:30190309"
FT TRANSMEM 161..182
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:30190309"
FT TOPO_DOM 183..218
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:30190309"
FT DOMAIN 22..150
FT /note="Ig-like C2-type"
FT CARBOHYD 93
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:30765606,
FT ECO:0007744|PDB:6J8G, ECO:0007744|PDB:6J8H,
FT ECO:0007744|PDB:6J8I, ECO:0007744|PDB:6J8J"
FT CARBOHYD 110
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:30190309,
FT ECO:0000269|PubMed:30765606, ECO:0007744|PDB:6AGF,
FT ECO:0007744|PDB:6J8G, ECO:0007744|PDB:6J8H,
FT ECO:0007744|PDB:6J8I, ECO:0007744|PDB:6J8J"
FT CARBOHYD 114
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:30190309,
FT ECO:0000269|PubMed:30765606, ECO:0007744|PDB:6AGF,
FT ECO:0007744|PDB:6J8G, ECO:0007744|PDB:6J8H,
FT ECO:0007744|PDB:6J8I, ECO:0007744|PDB:6J8J"
FT CARBOHYD 135
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:30765606,
FT ECO:0007744|PDB:6J8G, ECO:0007744|PDB:6J8H,
FT ECO:0007744|PDB:6J8I, ECO:0007744|PDB:6J8J"
FT DISULFID 21..43
FT /evidence="ECO:0000269|PubMed:30190309,
FT ECO:0000269|PubMed:30765606, ECO:0007744|PDB:6AGF,
FT ECO:0007744|PDB:6J8G, ECO:0007744|PDB:6J8H,
FT ECO:0007744|PDB:6J8I, ECO:0007744|PDB:6J8J"
FT DISULFID 40..121
FT /evidence="ECO:0000269|PubMed:30190309,
FT ECO:0000269|PubMed:30765606, ECO:0007744|PDB:6AGF,
FT ECO:0007744|PDB:6J8G, ECO:0007744|PDB:6J8H,
FT ECO:0007744|PDB:6J8I, ECO:0007744|PDB:6J8J"
FT VAR_SEQ 150..218
FT /note="ANRDMASIVSEIMMYVLIVVLTIWLVAEMIYCYKKIAAATETAAQENASEYL
FT AITSESKENCTGVQVAE -> GESGAACPFTVTHRRARWRDRWQAVDRTGWLCAWPANR
FT PQQRAEGEGSSPSCPLQLWPLFLSSPRRGQSMPVPHRRSGYRTQLCHLCCMTSGRCLLS
FT LSQRVVLGLPGIIIRCVSRGVV (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14622265"
FT /id="VSP_041982"
FT VARIANT 25
FT /note="D -> N (probable disease-associated variant found in
FT a patient with idiopathic childhood epilepsy; de novo
FT mutation; loss of function in increasing sodium channel
FT activity; dbSNP:rs786205837)"
FT /evidence="ECO:0000269|PubMed:19522081,
FT ECO:0000269|PubMed:29992740"
FT /id="VAR_062523"
FT VARIANT 85
FT /note="R -> H (in ATFB13; the mutant results in highly
FT reduced sodium currents and altered channel gating when
FT coexpressed with SCN5A in a heterologous expression system;
FT dbSNP:rs16969925)"
FT /evidence="ECO:0000269|PubMed:19808477"
FT /id="VAR_070219"
FT VARIANT 87
FT /note="E -> Q (probable disease-associated variant found in
FT a patient with non-specific cardiac conduction defects;
FT dbSNP:rs121434627)"
FT /evidence="ECO:0000269|PubMed:18464934"
FT /id="VAR_062524"
FT VARIANT 106
FT /note="I -> T (in DEE52; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:23148524"
FT /id="VAR_078019"
FT VARIANT 121
FT /note="C -> W (in GEFS+1; can rescue the loss of function
FT and defective trafficking to cell membrane phenotype of the
FT SCN1A variant Thr-1852; dbSNP:rs104894718)"
FT /evidence="ECO:0000269|PubMed:17928445,
FT ECO:0000269|PubMed:9697698"
FT /id="VAR_010165"
FT VARIANT 125
FT /note="R -> C (in DEE52; severely decreased channel
FT localization at the cell membrane; dbSNP:rs1135401736)"
FT /evidence="ECO:0000269|PubMed:19710327"
FT /id="VAR_078020"
FT VARIANT 125
FT /note="R -> L (in GEFS+1; dbSNP:rs759839781)"
FT /evidence="ECO:0000269|PubMed:21040232"
FT /id="VAR_067341"
FT VARIANT 138
FT /note="V -> I (in dbSNP:rs72558029)"
FT /evidence="ECO:0000269|PubMed:19522081"
FT /id="VAR_062525"
FT VARIANT 153
FT /note="D -> N (in ATFB13; the mutant results in reduced
FT sodium currents when coexpressed with SCN5A in a
FT heterologous expression system; dbSNP:rs72550247)"
FT /evidence="ECO:0000269|PubMed:19808477"
FT /id="VAR_070220"
FT VARIANT 208
FT /note="K -> I (in dbSNP:rs780958012)"
FT /evidence="ECO:0000269|PubMed:19522081"
FT /id="VAR_062526"
FT VARIANT 211
FT /note="C -> Y (in dbSNP:rs150721582)"
FT /evidence="ECO:0000269|PubMed:19522081"
FT /id="VAR_062527"
FT VARIANT 213
FT /note="G -> D (in dbSNP:rs201209882)"
FT /evidence="ECO:0000269|PubMed:19522081"
FT /id="VAR_062528"
FT STRAND 29..31
FT /evidence="ECO:0007829|PDB:6AGF"
FT STRAND 36..38
FT /evidence="ECO:0007829|PDB:6AGF"
FT STRAND 49..51
FT /evidence="ECO:0007829|PDB:6AGF"
FT STRAND 57..60
FT /evidence="ECO:0007829|PDB:6AGF"
FT STRAND 62..65
FT /evidence="ECO:0007829|PDB:6AGF"
FT STRAND 68..72
FT /evidence="ECO:0007829|PDB:6AGF"
FT STRAND 75..77
FT /evidence="ECO:0007829|PDB:6AGF"
FT STRAND 83..85
FT /evidence="ECO:0007829|PDB:6AGF"
FT STRAND 87..92
FT /evidence="ECO:0007829|PDB:6AGF"
FT STRAND 106..110
FT /evidence="ECO:0007829|PDB:6AGF"
FT HELIX 113..115
FT /evidence="ECO:0007829|PDB:6AGF"
FT STRAND 117..123
FT /evidence="ECO:0007829|PDB:6AGF"
FT STRAND 126..128
FT /evidence="ECO:0007829|PDB:6AGF"
FT STRAND 133..135
FT /evidence="ECO:0007829|PDB:6AGF"
FT STRAND 138..149
FT /evidence="ECO:0007829|PDB:6AGF"
FT HELIX 155..190
FT /evidence="ECO:0007829|PDB:6AGF"
SQ SEQUENCE 218 AA; 24707 MW; 09B812FA3F9E9018 CRC64;
MGRLLALVVG AALVSSACGG CVEVDSETEA VYGMTFKILC ISCKRRSETN AETFTEWTFR
QKGTEEFVKI LRYENEVLQL EEDERFEGRV VWNGSRGTKD LQDLSIFITN VTYNHSGDYE
CHVYRLLFFE NYEHNTSVVK KIHIEVVDKA NRDMASIVSE IMMYVLIVVL TIWLVAEMIY
CYKKIAAATE TAAQENASEY LAITSESKEN CTGVQVAE
