ID SCN3B_HUMAN Reviewed; 215 AA.
AC Q9NY72; A5H1I5; Q17RL3; Q9ULR2;
DT 11-JAN-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 27-MAR-2024, entry version 194.
DE RecName: Full=Sodium channel regulatory subunit beta-3 {ECO:0000305};
DE Flags: Precursor;
GN Name=SCN3B {ECO:0000312|HGNC:HGNC:20665}; Synonyms=KIAA1158;
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].
RC TISSUE=Brain;
RX PubMed=10688874; DOI=10.1073/pnas.030362197;
RA Morgan K., Stevens E.B., Shaw B., Cox P., Dixon A.K., Lee K., Pinnock R.D.,
RA Highes J., Richardson P.J., Mizuguchi K., Jackson A.P.;
RT "Beta3: an additional auxiliary subunit of the voltage-sensitive sodium
RT channel that modulates channel gating with distinct kinetics.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:2308-2313(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Amygdala;
RX PubMed=11230166; DOI=10.1101/gr.gr1547r;
RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S.,
RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J.,
RA Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W.,
RA Ottenwaelder B., Obermaier B., Tampe J., Heubner D., Wambutt R., Korn B.,
RA Klein M., Poustka A.;
RT "Towards a catalog of human genes and proteins: sequencing and analysis of
RT 500 novel complete protein coding human cDNAs.";
RL Genome Res. 11:422-435(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=10574461; DOI=10.1093/dnares/6.5.329;
RA Hirosawa M., Nagase T., Ishikawa K., Kikuno R., Nomura N., Ohara O.;
RT "Characterization of cDNA clones selected by the GeneMark analysis from
RT size-fractionated cDNA libraries from human brain.";
RL DNA Res. 6:329-336(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG NHLBI resequencing and genotyping service (RS&G);
RL Submitted (JUN-2006) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [7] {ECO:0007744|PDB:4L1D}
RP X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 25-145, SUBUNIT, SUBCELLULAR
RP LOCATION, DISULFIDE BONDS, GLYCOSYLATION, AND MUTAGENESIS OF CYS-48.
RX PubMed=24567321; DOI=10.1074/jbc.m113.527994;
RA Namadurai S., Balasuriya D., Rajappa R., Wiemhoefer M., Stott K.,
RA Klingauf J., Edwardson J.M., Chirgadze D.Y., Jackson A.P.;
RT "Crystal structure and molecular imaging of the Nav channel beta3 subunit
RT indicates a trimeric assembly.";
RL J. Biol. Chem. 289:10797-10811(2014).
RN [8] {ECO:0007744|PDB:7TJ8, ECO:0007744|PDB:7TJ9}
RP STRUCTURE BY ELECTRON MICROSCOPY (2.90 ANGSTROMS) IN COMPLEX WIRH SCN7A,
RP SUBUNIT, AND DISULFIDE BONDS.
RX PubMed=35301303; DOI=10.1038/s41467-022-28984-4;
RA Noland C.L., Chua H.C., Kschonsak M., Heusser S.A., Braun N., Chang T.,
RA Tam C., Tang J., Arthur C.P., Ciferri C., Pless S.A., Payandeh J.;
RT "Structure-guided unlocking of NaX reveals a non-selective tetrodotoxin-
RT sensitive cation channel.";
RL Nat. Commun. 13:1416-1416(2022).
RN [9]
RP VARIANTS [LARGE SCALE ANALYSIS] LEU-89 AND THR-195.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
RN [10]
RP VARIANT BRGDA7 PRO-10.
RX PubMed=20031595; DOI=10.1161/circgenetics.108.829192;
RA Hu D., Barajas-Martinez H., Burashnikov E., Springer M., Wu Y., Varro A.,
RA Pfeiffer R., Koopmann T.T., Cordeiro J.M., Guerchicoff A., Pollevick G.D.,
RA Antzelevitch C.;
RT "A mutation in the beta-3 subunit of the cardiac sodium channel associated
RT with Brugada ECG phenotype.";
RL Circ. Cardiovasc. Genet. 2:270-278(2009).
RN [11]
RP INVOLVEMENT IN ATFB16, VARIANT ATFB16 VAL-130, CHARACTERIZATION OF VARIANT
RP ATFB16 VAL-130, AND FUNCTION.
RX PubMed=20558140; DOI=10.1016/j.bbrc.2010.06.042;
RA Wang P., Yang Q., Wu X., Yang Y., Shi L., Wang C., Wu G., Xia Y., Yang B.,
RA Zhang R., Xu C., Cheng X., Li S., Zhao Y., Fu F., Liao Y., Fang F.,
RA Chen Q., Tu X., Wang Q.K.;
RT "Functional dominant-negative mutation of sodium channel subunit gene SCN3B
RT associated with atrial fibrillation in a Chinese GeneID population.";
RL Biochem. Biophys. Res. Commun. 398:98-104(2010).
RN [12]
RP VARIANT GLY-54.
RX PubMed=20042427; DOI=10.1093/cvr/cvp417;
RA Valdivia C.R., Medeiros-Domingo A., Ye B., Shen W.K., Algiers T.J.,
RA Ackerman M.J., Makielski J.C.;
RT "Loss-of-function mutation of the SCN3B-encoded sodium channel {beta}3
RT subunit associated with a case of idiopathic ventricular fibrillation.";
RL Cardiovasc. Res. 86:392-400(2010).
RN [13]
RP VARIANTS ATFB16 LYS-6; PRO-10 AND THR-161, CHARACTERIZATION OF VARIANTS
RP ATFB16 LYS-6; PRO-10 AND THR-161, FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=21051419; DOI=10.1093/cvr/cvq348;
RA Olesen M.S., Jespersen T., Nielsen J.B., Liang B., Moller D.V., Hedley P.,
RA Christiansen M., Varro A., Olesen S.P., Haunso S., Schmitt N.,
RA Svendsen J.H.;
RT "Mutations in sodium channel beta-subunit SCN3B are associated with early-
RT onset lone atrial fibrillation.";
RL Cardiovasc. Res. 89:786-793(2011).
CC -!- FUNCTION: Voltage-gated sodium channels regulatory subunit that
CC modulates channel gating kinetics (PubMed:20558140, PubMed:21051419).
CC Causes unique persistent sodium currents. Inactivates the sodium
CC channel opening more slowly than the subunit beta-1. Its association
CC with NFASC may target the sodium channels to the nodes of Ranvier of
CC developing axons and retain these channels at the nodes in mature
CC myelinated axons (By similarity). {ECO:0000250|UniProtKB:Q9JK00,
CC ECO:0000269|PubMed:20558140, ECO:0000269|PubMed:21051419}.
CC -!- SUBUNIT: Voltage-gated sodium channels are heterooligomeric complexes
CC consisting of ion conducting pore forming alpha subunits and regulatory
CC beta subunits. SCN3B is non-covalently associated with alpha subunits
CC and induces the formation of alpha subunit oligomers, including trimers
CC (PubMed:24567321, PubMed:35301303). Interacts with SCN10A. Interacts
CC with NFASC (By similarity). {ECO:0000250|UniProtKB:Q9JK00,
CC ECO:0000269|PubMed:24567321, ECO:0000269|PubMed:35301303}.
CC -!- INTERACTION:
CC Q9NY72; Q15848: ADIPOQ; NbExp=3; IntAct=EBI-17247926, EBI-10827839;
CC Q9NY72; Q9NRZ5: AGPAT4; NbExp=3; IntAct=EBI-17247926, EBI-1754287;
CC Q9NY72; Q9NUQ2: AGPAT5; NbExp=3; IntAct=EBI-17247926, EBI-6916385;
CC Q9NY72; Q86W74-2: ANKRD46; NbExp=3; IntAct=EBI-17247926, EBI-12109402;
CC Q9NY72; Q96PS8: AQP10; NbExp=3; IntAct=EBI-17247926, EBI-12820279;
CC Q9NY72; Q9H2C2: ARV1; NbExp=4; IntAct=EBI-17247926, EBI-11724186;
CC Q9NY72; Q9HD20-3: ATP13A1; NbExp=3; IntAct=EBI-17247926, EBI-12069500;
CC Q9NY72; P27449: ATP6V0C; NbExp=3; IntAct=EBI-17247926, EBI-721179;
CC Q9NY72; Q12981: BNIP1; NbExp=3; IntAct=EBI-17247926, EBI-4402847;
CC Q9NY72; Q12983: BNIP3; NbExp=3; IntAct=EBI-17247926, EBI-749464;
CC Q9NY72; Q6PL45-2: BRICD5; NbExp=3; IntAct=EBI-17247926, EBI-12244618;
CC Q9NY72; Q4LDR2: CTXN3; NbExp=3; IntAct=EBI-17247926, EBI-12019274;
CC Q9NY72; P78329: CYP4F2; NbExp=3; IntAct=EBI-17247926, EBI-1752413;
CC Q9NY72; P81534: DEFB103B; NbExp=3; IntAct=EBI-17247926, EBI-12074168;
CC Q9NY72; Q9BUN8: DERL1; NbExp=3; IntAct=EBI-17247926, EBI-398977;
CC Q9NY72; Q6ZPD8: DGAT2L6; NbExp=3; IntAct=EBI-17247926, EBI-12831978;
CC Q9NY72; Q9UKR5: ERG28; NbExp=3; IntAct=EBI-17247926, EBI-711490;
CC Q9NY72; Q96D05-2: FAM241B; NbExp=3; IntAct=EBI-17247926, EBI-12118888;
CC Q9NY72; Q92520: FAM3C; NbExp=3; IntAct=EBI-17247926, EBI-2876774;
CC Q9NY72; Q9Y3D6: FIS1; NbExp=3; IntAct=EBI-17247926, EBI-3385283;
CC Q9NY72; Q14318: FKBP8; NbExp=3; IntAct=EBI-17247926, EBI-724839;
CC Q9NY72; Q14802-3: FXYD3; NbExp=3; IntAct=EBI-17247926, EBI-12175685;
CC Q9NY72; Q8WWP7: GIMAP1; NbExp=3; IntAct=EBI-17247926, EBI-11991950;
CC Q9NY72; Q96F15: GIMAP5; NbExp=3; IntAct=EBI-17247926, EBI-6166686;
CC Q9NY72; Q8TDV0: GPR151; NbExp=3; IntAct=EBI-17247926, EBI-11955647;
CC Q9NY72; Q9BZJ8: GPR61; NbExp=3; IntAct=EBI-17247926, EBI-12808020;
CC Q9NY72; Q9Y5U9: IER3IP1; NbExp=3; IntAct=EBI-17247926, EBI-725665;
CC Q9NY72; Q9Y5U4: INSIG2; NbExp=3; IntAct=EBI-17247926, EBI-8503746;
CC Q9NY72; Q6H9L7: ISM2; NbExp=3; IntAct=EBI-17247926, EBI-17249161;
CC Q9NY72; P11215: ITGAM; NbExp=3; IntAct=EBI-17247926, EBI-2568251;
CC Q9NY72; Q68G75: LEMD1; NbExp=3; IntAct=EBI-17247926, EBI-12268900;
CC Q9NY72; O95214: LEPROTL1; NbExp=3; IntAct=EBI-17247926, EBI-750776;
CC Q9NY72; Q9UBY5: LPAR3; NbExp=3; IntAct=EBI-17247926, EBI-12033434;
CC Q9NY72; Q969L2: MAL2; NbExp=3; IntAct=EBI-17247926, EBI-944295;
CC Q9NY72; Q9P0N8: MARCHF2; NbExp=3; IntAct=EBI-17247926, EBI-10317612;
CC Q9NY72; Q6N075: MFSD5; NbExp=3; IntAct=EBI-17247926, EBI-3920969;
CC Q9NY72; O14880: MGST3; NbExp=3; IntAct=EBI-17247926, EBI-724754;
CC Q9NY72; Q5J8X5: MS4A13; NbExp=3; IntAct=EBI-17247926, EBI-12070086;
CC Q9NY72; Q9NZG7: NINJ2; NbExp=3; IntAct=EBI-17247926, EBI-10317425;
CC Q9NY72; Q9P0S3: ORMDL1; NbExp=3; IntAct=EBI-17247926, EBI-1054848;
CC Q9NY72; Q53FV1: ORMDL2; NbExp=3; IntAct=EBI-17247926, EBI-11075081;
CC Q9NY72; Q8NHP8: PLBD2; NbExp=3; IntAct=EBI-17247926, EBI-10968883;
CC Q9NY72; Q04941: PLP2; NbExp=3; IntAct=EBI-17247926, EBI-608347;
CC Q9NY72; Q96GM1: PLPPR2; NbExp=3; IntAct=EBI-17247926, EBI-12955265;
CC Q9NY72; Q01453: PMP22; NbExp=3; IntAct=EBI-17247926, EBI-2845982;
CC Q9NY72; Q02161-2: RHD; NbExp=3; IntAct=EBI-17247926, EBI-17249212;
CC Q9NY72; O76064: RNF8; NbExp=3; IntAct=EBI-17247926, EBI-373337;
CC Q9NY72; Q96GQ5: RUSF1; NbExp=3; IntAct=EBI-17247926, EBI-8636004;
CC Q9NY72; Q9NTJ5: SACM1L; NbExp=3; IntAct=EBI-17247926, EBI-3917235;
CC Q9NY72; O00767: SCD; NbExp=3; IntAct=EBI-17247926, EBI-2684237;
CC Q9NY72; Q96IW7: SEC22A; NbExp=3; IntAct=EBI-17247926, EBI-8652744;
CC Q9NY72; Q8N6R1: SERP2; NbExp=3; IntAct=EBI-17247926, EBI-749270;
CC Q9NY72; Q8WV19: SFT2D1; NbExp=3; IntAct=EBI-17247926, EBI-2854842;
CC Q9NY72; Q9H9B4: SFXN1; NbExp=3; IntAct=EBI-17247926, EBI-355861;
CC Q9NY72; Q9BWM7: SFXN3; NbExp=4; IntAct=EBI-17247926, EBI-1171999;
CC Q9NY72; P22732: SLC2A5; NbExp=3; IntAct=EBI-17247926, EBI-2825135;
CC Q9NY72; Q99726: SLC30A3; NbExp=3; IntAct=EBI-17247926, EBI-10294651;
CC Q9NY72; Q8IWU4: SLC30A8; NbExp=3; IntAct=EBI-17247926, EBI-10262251;
CC Q9NY72; Q96G79: SLC35A4; NbExp=3; IntAct=EBI-17247926, EBI-12363689;
CC Q9NY72; Q6ICL7: SLC35E4; NbExp=3; IntAct=EBI-17247926, EBI-12867720;
CC Q9NY72; Q9H2H9: SLC38A1; NbExp=3; IntAct=EBI-17247926, EBI-9978441;
CC Q9NY72; Q9NVC3: SLC38A7; NbExp=3; IntAct=EBI-17247926, EBI-10314552;
CC Q9NY72; P30825: SLC7A1; NbExp=3; IntAct=EBI-17247926, EBI-4289564;
CC Q9NY72; Q9NRQ5: SMCO4; NbExp=3; IntAct=EBI-17247926, EBI-8640191;
CC Q9NY72; B2RUZ4: SMIM1; NbExp=3; IntAct=EBI-17247926, EBI-12188413;
CC Q9NY72; P0DN84: STRIT1; NbExp=3; IntAct=EBI-17247926, EBI-12200293;
CC Q9NY72; Q13277: STX3; NbExp=3; IntAct=EBI-17247926, EBI-1394295;
CC Q9NY72; O43752: STX6; NbExp=3; IntAct=EBI-17247926, EBI-2695795;
CC Q9NY72; Q9UNK0: STX8; NbExp=3; IntAct=EBI-17247926, EBI-727240;
CC Q9NY72; Q9UPZ6: THSD7A; NbExp=3; IntAct=EBI-17247926, EBI-310962;
CC Q9NY72; O14925: TIMM23; NbExp=3; IntAct=EBI-17247926, EBI-1047996;
CC Q9NY72; Q9BZW4: TM6SF2; NbExp=3; IntAct=EBI-17247926, EBI-13082040;
CC Q9NY72; P55061: TMBIM6; NbExp=3; IntAct=EBI-17247926, EBI-1045825;
CC Q9NY72; Q9BXJ8: TMEM120A; NbExp=3; IntAct=EBI-17247926, EBI-727322;
CC Q9NY72; A0PK00: TMEM120B; NbExp=3; IntAct=EBI-17247926, EBI-10171534;
CC Q9NY72; Q5BJH2-2: TMEM128; NbExp=3; IntAct=EBI-17247926, EBI-10694905;
CC Q9NY72; Q9NV12: TMEM140; NbExp=3; IntAct=EBI-17247926, EBI-2844246;
CC Q9NY72; Q9Y6G1: TMEM14A; NbExp=3; IntAct=EBI-17247926, EBI-2800360;
CC Q9NY72; Q9NUH8: TMEM14B; NbExp=3; IntAct=EBI-17247926, EBI-8638294;
CC Q9NY72; Q9BTX3: TMEM208; NbExp=3; IntAct=EBI-17247926, EBI-12876824;
CC Q9NY72; Q8WW34-2: TMEM239; NbExp=3; IntAct=EBI-17247926, EBI-11528917;
CC Q9NY72; Q9BU79: TMEM243; NbExp=3; IntAct=EBI-17247926, EBI-12887458;
CC Q9NY72; Q69YG0: TMEM42; NbExp=3; IntAct=EBI-17247926, EBI-12038591;
CC Q9NY72; P56557: TMEM50B; NbExp=3; IntAct=EBI-17247926, EBI-12366453;
CC Q9NY72; Q9H2L4: TMEM60; NbExp=3; IntAct=EBI-17247926, EBI-2852148;
CC Q9NY72; Q6PI78: TMEM65; NbExp=3; IntAct=EBI-17247926, EBI-6656213;
CC Q9NY72; Q8N2M4: TMEM86A; NbExp=3; IntAct=EBI-17247926, EBI-12015604;
CC Q9NY72; Q6ZT21: TMPPE; NbExp=3; IntAct=EBI-17247926, EBI-11724433;
CC Q9NY72; Q6ZUI0: TPRG1; NbExp=3; IntAct=EBI-17247926, EBI-17249488;
CC Q9NY72; O60636: TSPAN2; NbExp=3; IntAct=EBI-17247926, EBI-3914288;
CC Q9NY72; A5PKU2: TUSC5; NbExp=3; IntAct=EBI-17247926, EBI-11988865;
CC Q9NY72; Q9NYZ1: TVP23B; NbExp=3; IntAct=EBI-17247926, EBI-11343401;
CC Q9NY72; Q9Y5Z9: UBIAD1; NbExp=3; IntAct=EBI-17247926, EBI-2819725;
CC Q9NY72; Q9NZ43: USE1; NbExp=3; IntAct=EBI-17247926, EBI-742842;
CC Q9NY72; P23763-3: VAMP1; NbExp=3; IntAct=EBI-17247926, EBI-12097582;
CC Q9NY72; P63027: VAMP2; NbExp=3; IntAct=EBI-17247926, EBI-520113;
CC Q9NY72; Q15836: VAMP3; NbExp=3; IntAct=EBI-17247926, EBI-722343;
CC Q9NY72; Q9P0L0: VAPA; NbExp=3; IntAct=EBI-17247926, EBI-1059156;
CC Q9NY72; O95292: VAPB; NbExp=3; IntAct=EBI-17247926, EBI-1188298;
CC Q9NY72; O95070: YIF1A; NbExp=3; IntAct=EBI-17247926, EBI-2799703;
CC Q9NY72; Q9BSR8: YIPF4; NbExp=3; IntAct=EBI-17247926, EBI-751253;
CC Q9NY72; O95159: ZFPL1; NbExp=3; IntAct=EBI-17247926, EBI-718439;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:24567321};
CC Single-pass type I membrane protein {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Expressed in the atrium.
CC {ECO:0000269|PubMed:21051419}.
CC -!- PTM: Intramolecular disulfide bonds favor the voltage-gated sodium
CC channel oligomeric complex assembly. {ECO:0000269|PubMed:24567321}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:24567321}.
CC -!- DISEASE: Brugada syndrome 7 (BRGDA7) [MIM:613120]: 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:20031595}.
CC Note=The gene represented in this entry may be involved in disease
CC pathogenesis.
CC -!- DISEASE: Atrial fibrillation, familial, 16 (ATFB16) [MIM:613120]: 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:20558140,
CC ECO:0000269|PubMed:21051419}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the sodium channel auxiliary subunit SCN3B (TC
CC 8.A.17) family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA86472.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AJ243396; CAB76825.1; -; mRNA.
DR EMBL; AL136589; CAB66524.1; -; mRNA.
DR EMBL; AB032984; BAA86472.1; ALT_INIT; mRNA.
DR EMBL; AK314513; BAG37113.1; -; mRNA.
DR EMBL; DQ677666; ABQ01237.1; -; Genomic_DNA.
DR EMBL; BC117282; AAI17283.1; -; mRNA.
DR EMBL; BC126265; AAI26266.1; -; mRNA.
DR CCDS; CCDS8442.1; -.
DR RefSeq; NP_001035241.1; NM_001040151.1.
DR RefSeq; NP_060870.1; NM_018400.3.
DR RefSeq; XP_011541199.1; XM_011542897.1.
DR PDB; 4L1D; X-ray; 2.50 A; A/B/C=25-145.
DR PDB; 7TJ8; EM; 3.20 A; B=1-215.
DR PDB; 7TJ9; EM; 2.90 A; B=1-215.
DR PDBsum; 4L1D; -.
DR PDBsum; 7TJ8; -.
DR PDBsum; 7TJ9; -.
DR AlphaFoldDB; Q9NY72; -.
DR EMDB; EMD-25919; -.
DR EMDB; EMD-25920; -.
DR SMR; Q9NY72; -.
DR BioGRID; 120912; 207.
DR IntAct; Q9NY72; 168.
DR MINT; Q9NY72; -.
DR STRING; 9606.ENSP00000376523; -.
DR DrugBank; DB05541; Brivaracetam.
DR DrugBank; DB00907; Cocaine.
DR DrugBank; DB13269; Dichlorobenzyl alcohol.
DR DrugBank; DB13961; Fish oil.
DR DrugBank; DB00776; Oxcarbazepine.
DR DrugBank; DB00243; Ranolazine.
DR DrugBank; DB00313; Valproic acid.
DR DrugBank; DB00909; Zonisamide.
DR DrugCentral; Q9NY72; -.
DR GlyCosmos; Q9NY72; 4 sites, No reported glycans.
DR GlyGen; Q9NY72; 4 sites.
DR PhosphoSitePlus; Q9NY72; -.
DR BioMuta; SCN3B; -.
DR DMDM; 12229762; -.
DR MassIVE; Q9NY72; -.
DR PaxDb; 9606-ENSP00000376523; -.
DR PeptideAtlas; Q9NY72; -.
DR ProteomicsDB; 83185; -.
DR Antibodypedia; 18943; 156 antibodies from 23 providers.
DR DNASU; 55800; -.
DR Ensembl; ENST00000299333.8; ENSP00000299333.3; ENSG00000166257.10.
DR Ensembl; ENST00000392770.6; ENSP00000376523.2; ENSG00000166257.10.
DR Ensembl; ENST00000530277.5; ENSP00000432785.1; ENSG00000166257.10.
DR Ensembl; ENST00000657123.1; ENSP00000499439.1; ENSG00000166257.10.
DR Ensembl; ENST00000657191.1; ENSP00000499755.1; ENSG00000166257.10.
DR GeneID; 55800; -.
DR KEGG; hsa:55800; -.
DR MANE-Select; ENST00000299333.8; ENSP00000299333.3; NM_001040151.2; NP_001035241.1.
DR UCSC; uc001pza.2; human.
DR AGR; HGNC:20665; -.
DR CTD; 55800; -.
DR DisGeNET; 55800; -.
DR GeneCards; SCN3B; -.
DR GeneReviews; SCN3B; -.
DR HGNC; HGNC:20665; SCN3B.
DR HPA; ENSG00000166257; Tissue enhanced (brain, pituitary gland).
DR MalaCards; SCN3B; -.
DR MIM; 608214; gene.
DR MIM; 613120; phenotype.
DR neXtProt; NX_Q9NY72; -.
DR OpenTargets; ENSG00000166257; -.
DR Orphanet; 130; Brugada syndrome.
DR Orphanet; 334; Familial atrial fibrillation.
DR PharmGKB; PA130546912; -.
DR VEuPathDB; HostDB:ENSG00000166257; -.
DR eggNOG; ENOG502QWH0; Eukaryota.
DR GeneTree; ENSGT00390000018560; -.
DR HOGENOM; CLU_096296_1_0_1; -.
DR InParanoid; Q9NY72; -.
DR OMA; QGSHMKL; -.
DR OrthoDB; 3036301at2759; -.
DR PhylomeDB; Q9NY72; -.
DR TreeFam; TF332097; -.
DR PathwayCommons; Q9NY72; -.
DR Reactome; R-HSA-445095; Interaction between L1 and Ankyrins.
DR Reactome; R-HSA-5576892; Phase 0 - rapid depolarisation.
DR SignaLink; Q9NY72; -.
DR BioGRID-ORCS; 55800; 16 hits in 1157 CRISPR screens.
DR GeneWiki; SCN3B; -.
DR GenomeRNAi; 55800; -.
DR Pharos; Q9NY72; Tbio.
DR PRO; PR:Q9NY72; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q9NY72; Protein.
DR Bgee; ENSG00000166257; Expressed in middle temporal gyrus and 127 other cell types or tissues.
DR ExpressionAtlas; Q9NY72; baseline and differential.
DR Genevisible; Q9NY72; HS.
DR GO; GO:0016020; C:membrane; NAS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:LIFEdb.
DR GO; GO:0001518; C:voltage-gated sodium channel complex; IDA:BHF-UCL.
DR GO; GO:0030018; C:Z disc; ISS:BHF-UCL.
DR GO; GO:0019871; F:sodium channel inhibitor activity; IBA:GO_Central.
DR GO; GO:0017080; F:sodium channel regulator activity; IDA:BHF-UCL.
DR GO; GO:0044325; F:transmembrane transporter binding; IPI:BHF-UCL.
DR GO; GO:0086006; F:voltage-gated sodium channel activity involved in cardiac muscle cell action potential; IDA:BHF-UCL.
DR GO; GO:0086014; P:atrial cardiac muscle cell action potential; IMP: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:0051899; P:membrane depolarization; IDA:BHF-UCL.
DR GO; GO:0086010; P:membrane depolarization during action potential; IDA:BHF-UCL.
DR GO; GO:0086012; P:membrane depolarization during cardiac muscle cell action potential; IMP:BHF-UCL.
DR GO; GO:0007399; P:nervous system development; IEA:Ensembl.
DR GO; GO:0010460; P:positive regulation of heart rate; ISS:BHF-UCL.
DR GO; GO:0010765; P:positive regulation of sodium ion transport; IDA:BHF-UCL.
DR GO; GO:0072659; P:protein localization to plasma membrane; IMP: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; IMP:BHF-UCL.
DR GO; GO:0060373; P:regulation of ventricular cardiac muscle cell membrane depolarization; IMP:BHF-UCL.
DR GO; GO:0086015; P:SA node cell action potential; ISS:BHF-UCL.
DR GO; GO:0035725; P:sodium ion transmembrane transport; IDA:BHF-UCL.
DR GO; GO:0006814; P:sodium ion transport; NAS:UniProtKB.
DR GO; GO:0086005; P:ventricular cardiac muscle cell action potential; IMP:BHF-UCL.
DR Gene3D; 2.60.40.10; Immunoglobulins; 1.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR003599; Ig_sub.
DR InterPro; IPR013106; Ig_V-set.
DR InterPro; IPR027098; Na_channel_b1/b3.
DR PANTHER; PTHR10546; SODIUM CHANNEL SUBUNIT BETA-1 AND 3; 1.
DR PANTHER; PTHR10546:SF1; SODIUM CHANNEL SUBUNIT BETA-3; 1.
DR Pfam; PF07686; V-set; 1.
DR SMART; SM00409; IG; 1.
DR SUPFAM; SSF48726; Immunoglobulin; 1.
DR PROSITE; PS50835; IG_LIKE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Atrial fibrillation; Brugada syndrome; Cell membrane;
KW Disease variant; Disulfide bond; Glycoprotein; Immunoglobulin domain;
KW Ion channel; Ion transport; Membrane; Reference proteome; Signal; Sodium;
KW Sodium channel; Sodium transport; Transmembrane; Transmembrane helix;
KW Transport; Voltage-gated channel.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT CHAIN 23..215
FT /note="Sodium channel regulatory subunit beta-3"
FT /id="PRO_0000014933"
FT TOPO_DOM 23..159
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 160..180
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 181..215
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 32..154
FT /note="Ig-like C2-type"
FT CARBOHYD 95
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 109
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 113
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 121
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 26..48
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114,
FT ECO:0000269|PubMed:24567321, ECO:0000269|PubMed:35301303,
FT ECO:0007744|PDB:4L1D, ECO:0007744|PDB:7TJ9"
FT DISULFID 45..120
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114,
FT ECO:0000269|PubMed:24567321, ECO:0000269|PubMed:35301303,
FT ECO:0007744|PDB:4L1D, ECO:0007744|PDB:7TJ9"
FT VARIANT 6
FT /note="R -> K (in ATFB16; affects steady-state channel
FT inactivation; dbSNP:rs587777558)"
FT /evidence="ECO:0000269|PubMed:21051419"
FT /id="VAR_071314"
FT VARIANT 10
FT /note="L -> P (in BRGDA7 and ATFB16; uncertain
FT significance; results in a decrease in peak sodium current
FT density; dbSNP:rs121918282)"
FT /evidence="ECO:0000269|PubMed:20031595,
FT ECO:0000269|PubMed:21051419"
FT /id="VAR_062529"
FT VARIANT 54
FT /note="V -> G (found in a case of idiopathic ventricular
FT fibrillation; uncertain significance; dbSNP:rs587777555)"
FT /evidence="ECO:0000269|PubMed:20042427"
FT /id="VAR_065232"
FT VARIANT 89
FT /note="Q -> L (in a colorectal cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_035521"
FT VARIANT 97
FT /note="S -> N (in dbSNP:rs35174956)"
FT /id="VAR_049928"
FT VARIANT 130
FT /note="A -> V (in ATFB16; results in decreased sodium
FT current density; dbSNP:rs587777556)"
FT /evidence="ECO:0000269|PubMed:20558140"
FT /id="VAR_071315"
FT VARIANT 161
FT /note="M -> T (in ATFB16; results in a decrease in peak
FT sodium current density; dbSNP:rs587777557)"
FT /evidence="ECO:0000269|PubMed:21051419"
FT /id="VAR_071316"
FT VARIANT 195
FT /note="A -> T (in a colorectal cancer sample; somatic
FT mutation; dbSNP:rs375755770)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_035522"
FT MUTAGEN 48
FT /note="C->A: Decreased voltage-gated sodium channel
FT oligomeric complex assembly."
FT /evidence="ECO:0000269|PubMed:24567321"
FT STRAND 34..36
FT /evidence="ECO:0007829|PDB:4L1D"
FT STRAND 41..43
FT /evidence="ECO:0007829|PDB:4L1D"
FT STRAND 57..65
FT /evidence="ECO:0007829|PDB:4L1D"
FT STRAND 66..68
FT /evidence="ECO:0007829|PDB:7TJ8"
FT STRAND 72..82
FT /evidence="ECO:0007829|PDB:4L1D"
FT TURN 87..90
FT /evidence="ECO:0007829|PDB:4L1D"
FT STRAND 91..94
FT /evidence="ECO:0007829|PDB:4L1D"
FT STRAND 100..102
FT /evidence="ECO:0007829|PDB:4L1D"
FT STRAND 105..107
FT /evidence="ECO:0007829|PDB:4L1D"
FT HELIX 112..114
FT /evidence="ECO:0007829|PDB:4L1D"
FT STRAND 116..125
FT /evidence="ECO:0007829|PDB:4L1D"
FT STRAND 135..145
FT /evidence="ECO:0007829|PDB:4L1D"
FT HELIX 153..185
FT /evidence="ECO:0007829|PDB:7TJ9"
SQ SEQUENCE 215 AA; 24702 MW; 70F6C604E9E26662 CRC64;
MPAFNRLFPL ASLVLIYWVS VCFPVCVEVP SETEAVQGNP MKLRCISCMK REEVEATTVV
EWFYRPEGGK DFLIYEYRNG HQEVESPFQG RLQWNGSKDL QDVSITVLNV TLNDSGLYTC
NVSREFEFEA HRPFVKTTRL IPLRVTEEAG EDFTSVVSEI MMYILLVFLT LWLLIEMIYC
YRKVSKAEEA AQENASDYLA IPSENKENSA VPVEE
//
