SCN5A_RAT
ID SCN5A_RAT Reviewed; 2019 AA.
AC P15389; Q925G6;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1990, sequence version 1.
DT 03-AUG-2022, entry version 159.
DE RecName: Full=Sodium channel protein type 5 subunit alpha;
DE AltName: Full=Sodium channel protein cardiac muscle subunit alpha;
DE AltName: Full=Sodium channel protein type V subunit alpha;
DE AltName: Full=Voltage-gated sodium channel subunit alpha Nav1.5;
GN Name=Scn5a;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Heart;
RX PubMed=2554302; DOI=10.1073/pnas.86.20.8170;
RA Rogart R.B., Cribbs L.L., Muglia L.K., Kephart D.D., Kaiser M.W.;
RT "Molecular cloning of a putative tetrodotoxin-resistant rat heart Na+
RT channel isoform.";
RL Proc. Natl. Acad. Sci. U.S.A. 86:8170-8174(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC STRAIN=Sprague-Dawley;
RA Korsgaard M.P.G., Christophersen P., Ahring P.K., Olesen S.;
RT "Characterisation of the novel voltage-gated Na+ channel rNav1.5a isolated
RT from the rat hippocampal progenitor stem cell line HiB5.";
RL Submitted (FEB-2001) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP MUTAGENESIS OF ASP-1612.
RX PubMed=9417050; DOI=10.1074/jbc.273.1.80;
RA Benzinger G.R., Kyle J.W., Blumenthal K.M., Hanck D.A.;
RT "A specific interaction between the cardiac sodium channel and site-3 toxin
RT anthopleurin B.";
RL J. Biol. Chem. 273:80-84(1998).
RN [4]
RP SUBCELLULAR LOCATION.
RX PubMed=15579534; DOI=10.1073/pnas.0403711101;
RA Mohler P.J., Rivolta I., Napolitano C., LeMaillet G., Lambert S.,
RA Priori S.G., Bennett V.;
RT "Nav1.5 E1053K mutation causing Brugada syndrome blocks binding to ankyrin-
RT G and expression of Nav1.5 on the surface of cardiomyocytes.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:17533-17538(2004).
RN [5]
RP ALTERNATIVE SPLICING, AND TISSUE SPECIFICITY.
RX PubMed=18386309; DOI=10.1080/01677060701672077;
RA Wang J., Ou S.-W., Wang Y.-J., Zong Z.-H., Lin L., Kameyama M.,
RA Kameyama A.;
RT "New variants of Nav1.5/SCN5A encode Na+ channels in the brain.";
RL J. Neurogenet. 22:57-75(2008).
RN [6]
RP ALTERNATIVE SPLICING, AND TISSUE SPECIFICITY.
RX PubMed=19376164; DOI=10.1016/j.neures.2009.04.003;
RA Wang J., Ou S.-W., Wang Y.-J., Kameyama M., Kameyama A., Zong Z.-H.;
RT "Analysis of four novel variants of Nav1.5/SCN5A cloned from the brain.";
RL Neurosci. Res. 64:339-347(2009).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-484; SER-485 AND THR-487, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
RN [8]
RP MUTAGENESIS OF LEU-869.
RX PubMed=24497506; DOI=10.1073/pnas.1324189111;
RA Gajewiak J., Azam L., Imperial J., Walewska A., Green B.R.,
RA Bandyopadhyay P.K., Raghuraman S., Ueberheide B., Bern M., Zhou H.M.,
RA Minassian N.A., Hagan R.H., Flinspach M., Liu Y., Bulaj G., Wickenden A.D.,
RA Olivera B.M., Yoshikami D., Zhang M.M.;
RT "A disulfide tether stabilizes the block of sodium channels by the
RT conotoxin muO[section sign]-GVIIJ.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:2758-2763(2014).
RN [9]
RP SITE CYS-374.
RX PubMed=26039939; DOI=10.1021/acs.biochem.5b00390;
RA Zhang M.M., Gajewiak J., Azam L., Bulaj G., Olivera B.M., Yoshikami D.;
RT "Probing the redox states of sodium channel cysteines at the binding site
RT of muO[section sign]-conotoxin GVIIJ.";
RL Biochemistry 54:3911-3920(2015).
CC -!- FUNCTION: This protein mediates the voltage-dependent sodium ion
CC permeability of excitable membranes. Assuming opened or closed
CC conformations in response to the voltage difference across the
CC membrane, the protein forms a sodium-selective channel through which
CC Na(+) ions may pass in accordance with their electrochemical gradient.
CC It is a tetrodotoxin-resistant Na(+) channel isoform. This channel is
CC responsible for the initial upstroke of the action potential. Channel
CC inactivation is regulated by intracellular calcium levels.
CC {ECO:0000250|UniProtKB:Q14524, ECO:0000250|UniProtKB:Q9JJV9}.
CC -!- SUBUNIT: Interacts with the PDZ domain of the syntrophin SNTA1, SNTB1
CC and SNTB2. Interacts with NEDD4, NEDD4L, WWP2 and GPD1L. Interacts with
CC CALM. Interacts with FGF13; the interaction is direct and may regulate
CC SNC5A density at membranes and function. May also interact with FGF12
CC and FGF14. Interacts with ANK3 (By similarity).
CC {ECO:0000250|UniProtKB:Q14524, ECO:0000250|UniProtKB:Q9JJV9}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q14524};
CC Multi-pass membrane protein {ECO:0000250|UniProtKB:D0E0C2}. Cytoplasm,
CC perinuclear region {ECO:0000250|UniProtKB:Q14524}. Cell membrane,
CC sarcolemma, T-tubule {ECO:0000269|PubMed:15579534}. Note=RANGRF
CC promotes trafficking to the cell membrane.
CC {ECO:0000250|UniProtKB:Q14524}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P15389-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P15389-2; Sequence=VSP_037482;
CC -!- TISSUE SPECIFICITY: Strongly expressed in the heart. Also expressed in
CC adult and fetal brain, spinal cord, testis, and at moderate levels in
CC kidney, adrenal gland, lung, skeletal muscle, spleen, stomach and
CC bladder. Isoform 2 is expressed in brain. {ECO:0000269|PubMed:18386309,
CC ECO:0000269|PubMed:19376164}.
CC -!- DOMAIN: The sequence contains 4 internal repeats, each with 5
CC hydrophobic segments (S1, S2, S3, S5, S6) and one positively charged
CC segment (S4). Segments S4 are probably the voltage-sensors and are
CC characterized by a series of positively charged amino acids at every
CC third position. {ECO:0000305}.
CC -!- DOMAIN: The IQ domain mediates association with calmodulin.
CC {ECO:0000250|UniProtKB:Q14524}.
CC -!- PTM: Phosphorylation at Ser-1505 by PKC in a highly conserved
CC cytoplasmic loop slows inactivation of the sodium channel and reduces
CC peak sodium currents. Regulated through phosphorylation by CaMK2D.
CC {ECO:0000250|UniProtKB:Q14524, ECO:0000250|UniProtKB:Q9JJV9}.
CC -!- PTM: Ubiquitinated by NEDD4L; which promotes its endocytosis. Does not
CC seem to be ubiquitinated by NEDD4 or WWP2.
CC {ECO:0000250|UniProtKB:Q14524}.
CC -!- PTM: Lacks the cysteine which covalently binds the conotoxin GVIIJ.
CC This cysteine (position 869) is speculated in other sodium channel
CC subunits alpha to be implied in covalent binding with the sodium
CC channel subunit beta-2 or beta-4. {ECO:0000305|PubMed:24497506}.
CC -!- MISCELLANEOUS: Na(+) channels in mammalian cardiac membrane have
CC functional properties quite distinct from Na(+) channels in nerve and
CC skeletal muscle.
CC -!- SIMILARITY: Belongs to the sodium channel (TC 1.A.1.10) family.
CC Nav1.5/SCN5A subfamily. {ECO:0000305}.
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DR EMBL; M27902; AAA42114.1; -; mRNA.
DR EMBL; AF353637; AAK38884.1; -; mRNA.
DR PIR; A33996; A33996.
DR RefSeq; NP_001153634.1; NM_001160162.1. [P15389-2]
DR RefSeq; NP_037257.1; NM_013125.2. [P15389-1]
DR PDB; 6UZ0; EM; 3.24 A; A=1-1898.
DR PDB; 6UZ3; EM; 3.50 A; A=1-1898.
DR PDB; 7FBS; EM; 3.40 A; A=1-1898.
DR PDB; 7K18; EM; 3.30 A; A=1-1898.
DR PDBsum; 6UZ0; -.
DR PDBsum; 6UZ3; -.
DR PDBsum; 7FBS; -.
DR PDBsum; 7K18; -.
DR AlphaFoldDB; P15389; -.
DR BMRB; P15389; -.
DR SMR; P15389; -.
DR BioGRID; 247694; 1.
DR DIP; DIP-60063N; -.
DR IntAct; P15389; 2.
DR STRING; 10116.ENSRNOP00000060180; -.
DR BindingDB; P15389; -.
DR ChEMBL; CHEMBL3866; -.
DR DrugCentral; P15389; -.
DR GuidetoPHARMACOLOGY; 582; -.
DR GlyGen; P15389; 13 sites.
DR iPTMnet; P15389; -.
DR PhosphoSitePlus; P15389; -.
DR SwissPalm; P15389; -.
DR PaxDb; P15389; -.
DR PRIDE; P15389; -.
DR ABCD; P15389; 2 sequenced antibodies.
DR GeneID; 25665; -.
DR KEGG; rno:25665; -.
DR UCSC; RGD:3637; rat. [P15389-1]
DR CTD; 6331; -.
DR RGD; 3637; Scn5a.
DR eggNOG; KOG2301; Eukaryota.
DR InParanoid; P15389; -.
DR PhylomeDB; P15389; -.
DR Reactome; R-RNO-5576892; Phase 0 - rapid depolarisation.
DR PRO; PR:P15389; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005901; C:caveola; ISS:BHF-UCL.
DR GO; GO:0009986; C:cell surface; ISO:RGD.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:BHF-UCL.
DR GO; GO:0016021; C:integral component of membrane; ISS:UniProtKB.
DR GO; GO:0014704; C:intercalated disc; IDA:BHF-UCL.
DR GO; GO:0016328; C:lateral plasma membrane; ISO:RGD.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; ISO:RGD.
DR GO; GO:0042383; C:sarcolemma; ISO:RGD.
DR GO; GO:0034706; C:sodium channel complex; ISO:RGD.
DR GO; GO:0030315; C:T-tubule; IDA:BHF-UCL.
DR GO; GO:0001518; C:voltage-gated sodium channel complex; ISS:BHF-UCL.
DR GO; GO:0030018; C:Z disc; ISS:BHF-UCL.
DR GO; GO:0030506; F:ankyrin binding; IDA:RGD.
DR GO; GO:0005516; F:calmodulin binding; ISO:RGD.
DR GO; GO:0019899; F:enzyme binding; ISO:RGD.
DR GO; GO:0017134; F:fibroblast growth factor binding; IPI:RGD.
DR GO; GO:0050998; F:nitric-oxide synthase binding; ISO:RGD.
DR GO; GO:0019904; F:protein domain specific binding; ISO:RGD.
DR GO; GO:0019901; F:protein kinase binding; ISO:RGD.
DR GO; GO:0097110; F:scaffold protein binding; ISO:RGD.
DR GO; GO:0044325; F:transmembrane transporter binding; ISO:RGD.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:RGD.
DR GO; GO:0005244; F:voltage-gated ion channel activity; IEA:UniProtKB-KW.
DR GO; GO:0005248; F:voltage-gated sodium channel activity; ISS:UniProtKB.
DR GO; GO:0086060; F:voltage-gated sodium channel activity involved in AV node cell action potential; ISS:BHF-UCL.
DR GO; GO:0086061; F:voltage-gated sodium channel activity involved in bundle of His cell action potential; ISS: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; ISS:BHF-UCL.
DR GO; GO:0086063; F:voltage-gated sodium channel activity involved in SA node cell action potential; ISS:BHF-UCL.
DR GO; GO:0086014; P:atrial cardiac muscle cell action potential; ISS:BHF-UCL.
DR GO; GO:0086016; P:AV node cell action potential; ISS:BHF-UCL.
DR GO; GO:0086067; P:AV node cell to bundle of His cell communication; ISS:BHF-UCL.
DR GO; GO:0003360; P:brainstem development; IEP:RGD.
DR GO; GO:0086043; P:bundle of His cell action potential; ISS:BHF-UCL.
DR GO; GO:0086002; P:cardiac muscle cell action potential involved in contraction; ISS:BHF-UCL.
DR GO; GO:0060048; P:cardiac muscle contraction; ISS:BHF-UCL.
DR GO; GO:0003231; P:cardiac ventricle development; ISO:RGD.
DR GO; GO:0071277; P:cellular response to calcium ion; ISS:UniProtKB.
DR GO; GO:0021549; P:cerebellum development; IEP:RGD.
DR GO; GO:0051899; P:membrane depolarization; ISS:BHF-UCL.
DR GO; GO:0086010; P:membrane depolarization during action potential; ISS:BHF-UCL.
DR GO; GO:0098912; P:membrane depolarization during atrial cardiac muscle cell action potential; ISO:RGD.
DR GO; GO:0086045; P:membrane depolarization during AV node cell action potential; ISS:BHF-UCL.
DR GO; GO:0086048; P:membrane depolarization during bundle of His cell action potential; ISS:BHF-UCL.
DR GO; GO:0086012; P:membrane depolarization during cardiac muscle cell action potential; IMP:BHF-UCL.
DR GO; GO:0086047; P:membrane depolarization during Purkinje myocyte cell action potential; ISS:BHF-UCL.
DR GO; GO:0086046; P:membrane depolarization during SA node cell action potential; ISS:BHF-UCL.
DR GO; GO:0019228; P:neuronal action potential; IBA:GO_Central.
DR GO; GO:0042475; P:odontogenesis of dentin-containing tooth; IEP:RGD.
DR GO; GO:0045760; P:positive regulation of action potential; IMP:RGD.
DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; IMP:RGD.
DR GO; GO:0010460; P:positive regulation of heart rate; IMP:RGD.
DR GO; GO:0010765; P:positive regulation of sodium ion transport; ISS:BHF-UCL.
DR GO; GO:0060371; P:regulation of atrial cardiac muscle cell membrane depolarization; ISS:BHF-UCL.
DR GO; GO:0060372; P:regulation of atrial cardiac muscle cell membrane repolarization; ISS:BHF-UCL.
DR GO; GO:0086004; P:regulation of cardiac muscle cell contraction; ISS:BHF-UCL.
DR GO; GO:0002027; P:regulation of heart rate; ISS:BHF-UCL.
DR GO; GO:0086091; P:regulation of heart rate by cardiac conduction; ISS:BHF-UCL.
DR GO; GO:1902305; P:regulation of sodium ion transmembrane transport; ISS:BHF-UCL.
DR GO; GO:0060373; P:regulation of ventricular cardiac muscle cell membrane depolarization; ISS:BHF-UCL.
DR GO; GO:0060307; P:regulation of ventricular cardiac muscle cell membrane repolarization; ISS:BHF-UCL.
DR GO; GO:0014894; P:response to denervation involved in regulation of muscle adaptation; IMP:RGD.
DR GO; GO:0014070; P:response to organic cyclic compound; ISO:RGD.
DR GO; GO:0086015; P:SA node cell action potential; ISS:BHF-UCL.
DR GO; GO:0098719; P:sodium ion import across plasma membrane; IMP:BHF-UCL.
DR GO; GO:0035725; P:sodium ion transmembrane transport; IMP:RGD.
DR GO; GO:0006814; P:sodium ion transport; ISS:UniProtKB.
DR GO; GO:0021537; P:telencephalon development; IEP:RGD.
DR GO; GO:0086005; P:ventricular cardiac muscle cell action potential; ISO:RGD.
DR CDD; cd13433; Na_channel_gate; 1.
DR Gene3D; 1.20.120.350; -; 4.
DR InterPro; IPR005821; Ion_trans_dom.
DR InterPro; IPR008053; Na_channel_a5su.
DR InterPro; IPR001696; Na_channel_asu.
DR InterPro; IPR044564; Na_chnl_inactivation_gate.
DR InterPro; IPR010526; Na_trans_assoc.
DR InterPro; IPR024583; Na_trans_cytopl.
DR InterPro; IPR043203; VGCC_Ca_Na.
DR InterPro; IPR027359; Volt_channel_dom_sf.
DR PANTHER; PTHR10037; PTHR10037; 1.
DR Pfam; PF00520; Ion_trans; 4.
DR Pfam; PF06512; Na_trans_assoc; 1.
DR Pfam; PF11933; Na_trans_cytopl; 1.
DR PRINTS; PR00170; NACHANNEL.
DR PRINTS; PR01666; NACHANNEL5.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Calmodulin-binding; Cell membrane;
KW Cytoplasm; Disulfide bond; Glycoprotein; Ion channel; Ion transport;
KW Membrane; Methylation; Phosphoprotein; Reference proteome; Repeat; Sodium;
KW Sodium channel; Sodium transport; Transmembrane; Transmembrane helix;
KW Transport; Ubl conjugation; Voltage-gated channel.
FT CHAIN 1..2019
FT /note="Sodium channel protein type 5 subunit alpha"
FT /id="PRO_0000048498"
FT TOPO_DOM 1..132
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 133..151
FT /note="Helical; Name=S1 of repeat I"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 152..158
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 159..179
FT /note="Helical; Name=S2 of repeat I"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 180..193
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 194..211
FT /note="Helical; Name=S3 of repeat I"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 212..217
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 218..234
FT /note="Helical; Name=S4 of repeat I"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 235..253
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 254..273
FT /note="Helical; Name=S5 of repeat I"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 274..358
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT INTRAMEM 359..383
FT /note="Pore-forming"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 384..390
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 391..411
FT /note="Helical; Name=S6 of repeat I"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 412..718
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 719..737
FT /note="Helical; Name=S1 of repeat II"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 738..748
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 749..768
FT /note="Helical; Name=S2 of repeat II"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 769..782
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 783..802
FT /note="Helical; Name=S3 of repeat II"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 803..804
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 805..822
FT /note="Helical; Name=S4 of repeat II"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 823..838
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 839..857
FT /note="Helical; Name=S5 of repeat II"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 858..886
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT INTRAMEM 887..907
FT /note="Pore-forming"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 908..920
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 921..941
FT /note="Helical; Name=S6 of repeat II"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 942..1208
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1209..1226
FT /note="Helical; Name=S1 of repeat III"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 1227..1239
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1240..1258
FT /note="Helical; Name=S2 of repeat III"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 1259..1272
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1273..1291
FT /note="Helical; Name=S3 of repeat III"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 1292..1299
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1300..1318
FT /note="Helical; Name=S4 of repeat III"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 1319..1335
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1336..1355
FT /note="Helical; Name=S5 of repeat III"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 1356..1407
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT INTRAMEM 1408..1429
FT /note="Pore-forming"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 1430..1446
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1447..1468
FT /note="Helical; Name=S6 of repeat III"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 1469..1531
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1532..1549
FT /note="Helical; Name=S1 of repeat IV"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 1550..1560
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1561..1579
FT /note="Helical; Name=S2 of repeat IV"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 1580..1591
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1592..1609
FT /note="Helical; Name=S3 of repeat IV"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 1610..1622
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1623..1639
FT /note="Helical; Name=S4 of repeat IV"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 1640..1658
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1659..1676
FT /note="Helical; Name=S5 of repeat IV"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 1677..1698
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT INTRAMEM 1699..1721
FT /note="Pore-forming"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 1722..1750
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1751..1773
FT /note="Helical; Name=S6 of repeat IV"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 1774..2019
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT REPEAT 114..421
FT /note="I"
FT /evidence="ECO:0000305"
FT REPEAT 700..972
FT /note="II"
FT /evidence="ECO:0000305"
FT REPEAT 1189..1503
FT /note="III"
FT /evidence="ECO:0000305"
FT REPEAT 1512..1809
FT /note="IV"
FT /evidence="ECO:0000305"
FT DOMAIN 1903..1932
FT /note="IQ"
FT REGION 27..64
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 462..588
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 618..655
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 996..1144
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1841..1903
FT /note="Interaction with FGF13"
FT /evidence="ECO:0000250|UniProtKB:Q14524"
FT REGION 1964..2019
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1977..1980
FT /note="Interaction with NEDD4, NEDD4L and WWP2"
FT /evidence="ECO:0000250|UniProtKB:Q14524"
FT COMPBIAS 481..501
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 504..527
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1021..1040
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1057..1071
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1096..1126
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1964..1995
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 374
FT /note="Cys residue near the selectivity filter, which has a
FT free thiol that is susceptible to reaction with
FT methanethiosulfonate (MTSET); Sodium current is
FT irreversibly blocked by MTSET"
FT /evidence="ECO:0000250|UniProtKB:P04775,
FT ECO:0000269|PubMed:26039939"
FT MOD_RES 37
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14524"
FT MOD_RES 39
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q14524"
FT MOD_RES 458
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14524"
FT MOD_RES 461
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14524"
FT MOD_RES 484
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 485
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 487
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 498
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14524"
FT MOD_RES 511
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14524"
FT MOD_RES 527
FT /note="Dimethylated arginine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q14524"
FT MOD_RES 527
FT /note="Omega-N-methylarginine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q14524"
FT MOD_RES 540
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9JJV9"
FT MOD_RES 572
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14524"
FT MOD_RES 665
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14524"
FT MOD_RES 668
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14524"
FT MOD_RES 1505
FT /note="Phosphoserine; by PKC"
FT /evidence="ECO:0000250|UniProtKB:Q14524"
FT CARBOHYD 215
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 284
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 289
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 292
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 319
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 329
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 741
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 804
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 865
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1367
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1376
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1382
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1390
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 281..336
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT DISULFID 909..918
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT VAR_SEQ 1080..1132
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_037482"
FT MUTAGEN 869
FT /note="L->C: >1000-fold increase of sensitivity to the
FT conotoxin GVIIJ(SSG)."
FT /evidence="ECO:0000269|PubMed:24497506"
FT MUTAGEN 1612
FT /note="D->N,R: Little change in voltage-dependence of
FT conductance and decrease in affinity to the sea anemone
FT toxin anthopleurin-B (residue Lys-37)."
FT /evidence="ECO:0000269|PubMed:9417050"
FT HELIX 120..130
FT /evidence="ECO:0007829|PDB:6UZ0"
FT HELIX 132..149
FT /evidence="ECO:0007829|PDB:6UZ0"
FT HELIX 158..180
FT /evidence="ECO:0007829|PDB:6UZ0"
FT HELIX 183..191
FT /evidence="ECO:0007829|PDB:6UZ0"
FT HELIX 193..210
FT /evidence="ECO:0007829|PDB:6UZ0"
FT HELIX 218..229
FT /evidence="ECO:0007829|PDB:6UZ0"
FT HELIX 230..233
FT /evidence="ECO:0007829|PDB:6UZ0"
FT HELIX 237..250
FT /evidence="ECO:0007829|PDB:6UZ0"
FT HELIX 252..273
FT /evidence="ECO:0007829|PDB:6UZ0"
FT HELIX 276..278
FT /evidence="ECO:0007829|PDB:6UZ0"
FT STRAND 280..283
FT /evidence="ECO:0007829|PDB:6UZ0"
FT STRAND 291..293
FT /evidence="ECO:0007829|PDB:7K18"
FT HELIX 304..309
FT /evidence="ECO:0007829|PDB:6UZ0"
FT HELIX 312..314
FT /evidence="ECO:0007829|PDB:7K18"
FT STRAND 321..324
FT /evidence="ECO:0007829|PDB:6UZ0"
FT STRAND 329..333
FT /evidence="ECO:0007829|PDB:6UZ0"
FT STRAND 340..344
FT /evidence="ECO:0007829|PDB:6UZ0"
FT STRAND 352..354
FT /evidence="ECO:0007829|PDB:6UZ0"
FT STRAND 356..358
FT /evidence="ECO:0007829|PDB:7K18"
FT HELIX 359..371
FT /evidence="ECO:0007829|PDB:6UZ0"
FT TURN 372..374
FT /evidence="ECO:0007829|PDB:6UZ0"
FT HELIX 375..385
FT /evidence="ECO:0007829|PDB:6UZ0"
FT HELIX 388..390
FT /evidence="ECO:0007829|PDB:6UZ0"
FT HELIX 391..400
FT /evidence="ECO:0007829|PDB:6UZ0"
FT HELIX 402..429
FT /evidence="ECO:0007829|PDB:6UZ0"
FT HELIX 701..714
FT /evidence="ECO:0007829|PDB:6UZ0"
FT HELIX 721..736
FT /evidence="ECO:0007829|PDB:6UZ0"
FT HELIX 744..769
FT /evidence="ECO:0007829|PDB:6UZ0"
FT HELIX 774..779
FT /evidence="ECO:0007829|PDB:6UZ0"
FT HELIX 781..797
FT /evidence="ECO:0007829|PDB:6UZ0"
FT HELIX 807..822
FT /evidence="ECO:0007829|PDB:6UZ0"
FT HELIX 824..836
FT /evidence="ECO:0007829|PDB:6UZ0"
FT TURN 837..840
FT /evidence="ECO:0007829|PDB:6UZ0"
FT HELIX 841..868
FT /evidence="ECO:0007829|PDB:6UZ0"
FT HELIX 870..872
FT /evidence="ECO:0007829|PDB:6UZ0"
FT STRAND 874..878
FT /evidence="ECO:0007829|PDB:6UZ0"
FT STRAND 884..887
FT /evidence="ECO:0007829|PDB:6UZ0"
FT HELIX 888..899
FT /evidence="ECO:0007829|PDB:6UZ0"
FT HELIX 903..912
FT /evidence="ECO:0007829|PDB:6UZ0"
FT HELIX 915..943
FT /evidence="ECO:0007829|PDB:6UZ0"
FT HELIX 1191..1204
FT /evidence="ECO:0007829|PDB:6UZ0"
FT HELIX 1207..1225
FT /evidence="ECO:0007829|PDB:6UZ0"
FT HELIX 1229..1231
FT /evidence="ECO:0007829|PDB:6UZ0"
FT HELIX 1235..1269
FT /evidence="ECO:0007829|PDB:6UZ0"
FT HELIX 1272..1292
FT /evidence="ECO:0007829|PDB:6UZ0"
FT STRAND 1297..1299
FT /evidence="ECO:0007829|PDB:6UZ0"
FT TURN 1300..1302
FT /evidence="ECO:0007829|PDB:6UZ0"
FT HELIX 1305..1314
FT /evidence="ECO:0007829|PDB:6UZ0"
FT HELIX 1315..1318
FT /evidence="ECO:0007829|PDB:6UZ0"
FT HELIX 1320..1330
FT /evidence="ECO:0007829|PDB:6UZ0"
FT HELIX 1333..1357
FT /evidence="ECO:0007829|PDB:6UZ0"
FT TURN 1359..1362
FT /evidence="ECO:0007829|PDB:7K18"
FT TURN 1368..1371
FT /evidence="ECO:0007829|PDB:6UZ0"
FT TURN 1377..1379
FT /evidence="ECO:0007829|PDB:6UZ0"
FT HELIX 1383..1389
FT /evidence="ECO:0007829|PDB:6UZ0"
FT STRAND 1405..1407
FT /evidence="ECO:0007829|PDB:6UZ0"
FT HELIX 1408..1419
FT /evidence="ECO:0007829|PDB:6UZ0"
FT STRAND 1420..1422
FT /evidence="ECO:0007829|PDB:6UZ3"
FT HELIX 1423..1430
FT /evidence="ECO:0007829|PDB:6UZ0"
FT STRAND 1435..1438
FT /evidence="ECO:0007829|PDB:6UZ0"
FT TURN 1442..1445
FT /evidence="ECO:0007829|PDB:7K18"
FT HELIX 1446..1448
FT /evidence="ECO:0007829|PDB:6UZ0"
FT HELIX 1449..1460
FT /evidence="ECO:0007829|PDB:6UZ0"
FT HELIX 1463..1482
FT /evidence="ECO:0007829|PDB:6UZ0"
FT HELIX 1491..1502
FT /evidence="ECO:0007829|PDB:6UZ0"
FT HELIX 1518..1528
FT /evidence="ECO:0007829|PDB:6UZ0"
FT HELIX 1530..1548
FT /evidence="ECO:0007829|PDB:6UZ0"
FT HELIX 1556..1581
FT /evidence="ECO:0007829|PDB:6UZ0"
FT STRAND 1583..1585
FT /evidence="ECO:0007829|PDB:6UZ0"
FT HELIX 1587..1590
FT /evidence="ECO:0007829|PDB:6UZ0"
FT HELIX 1592..1611
FT /evidence="ECO:0007829|PDB:6UZ0"
FT HELIX 1614..1617
FT /evidence="ECO:0007829|PDB:6UZ0"
FT HELIX 1623..1629
FT /evidence="ECO:0007829|PDB:6UZ0"
FT HELIX 1632..1635
FT /evidence="ECO:0007829|PDB:6UZ0"
FT HELIX 1636..1639
FT /evidence="ECO:0007829|PDB:6UZ0"
FT HELIX 1644..1680
FT /evidence="ECO:0007829|PDB:6UZ0"
FT TURN 1681..1683
FT /evidence="ECO:0007829|PDB:6UZ0"
FT STRAND 1692..1694
FT /evidence="ECO:0007829|PDB:6UZ0"
FT STRAND 1696..1698
FT /evidence="ECO:0007829|PDB:6UZ0"
FT HELIX 1699..1710
FT /evidence="ECO:0007829|PDB:6UZ0"
FT TURN 1711..1714
FT /evidence="ECO:0007829|PDB:6UZ0"
FT HELIX 1715..1723
FT /evidence="ECO:0007829|PDB:6UZ0"
FT TURN 1727..1729
FT /evidence="ECO:0007829|PDB:6UZ0"
FT STRAND 1737..1739
FT /evidence="ECO:0007829|PDB:6UZ0"
FT HELIX 1747..1779
FT /evidence="ECO:0007829|PDB:6UZ0"
SQ SEQUENCE 2019 AA; 227367 MW; CFC3B03CEAE708AD CRC64;
MANLLLPRGT SSFRRFTRES LAAIEKRMAE KQARGGSATS QESREGLQEE EAPRPQLDLQ
ASKKLPDLYG NPPRELIGEP LEDLDPFYST QKTFIVLNKG KTIFRFSATN ALYVLSPFHP
VRRAAVKILV HSLFSMLIMC TILTNCVFMA QHDPPPWTKY VEYTFTAIYT FESLVKILAR
GFCLHAFTFL RDPWNWLDFS VIVMAYTTEF VDLGNVSALR TFRVLRALKT ISVISGLKTI
VGALIQSVKK LADVMVLTVF CLSVFALIGL QLFMGNLRHK CVRNFTELNG TNGSVEADGL
VWNSLDVYLN DPANYLLKNG TTDVLLCGNS SDAGTCPEGY RCLKAGENPD HGYTSFDSFA
WAFLALFRLM TQDCWERLYQ QTLRSAGKIY MIFFMLVIFL GSFYLVNLIL AVVAMAYEEQ
NQATIAETEE KEKRFQEAME MLKKEHEALT IRGVDTVSRS SLEMSPLAPV TNHERKSKRR
KRLSSGTEDG GDDRLPKSDS EDGPRALNQL SLTHGLSRTS MRPRSSRGSI FTFRRRDQGS
EADFADDENS TAGESESHRT SLLVPWPLRH PSAQGQPGPG ASAPGYVLNG KRNSTVDCNG
VVSLLGAGDA EATSPGSYLL RPMVLDRPPD TTTPSEEPGG PQMLTPQAPC ADGFEEPGAR
QRALSAVSVL TSALEELEES HRKCPPCWNR FAQHYLIWEC CPLWMSIKQK VKFVVMDPFA
DLTITMCIVL NTLFMALEHY NMTAEFEEML QVGNLVFTGI FTAEMTFKII ALDPYYYFQQ
GWNIFDSIIV ILSLMELGLS RMGNLSVLRS FRLLRVFKLA KSWPTLNTLI KIIGNSVGAL
GNLTLVLAII VFIFAVVGMQ LFGKNYSELR HRISDSGLLP RWHMMDFFHA FLIIFRILCG
EWIETMWDCM EVSGQSLCLL VFLLVMVIGN LVVLNLFLAL LLSSFSADNL TAPDEDGEMN
NLQLALARIQ RGLRFVKRTT WDFCCGILRR RPKKPAALAT HSQLPSCITA PRSPPPPEVE
KVPPARKETR FEEDKRPGQG TPGDSEPVCV PIAVAESDTE DQEEDEENSL GTEEESSKQE
SQVVSGGHEP YQEPRAWSQV SETTSSEAGA STSQADWQQE QKTEPQAPGC GETPEDSYSE
GSTADMTNTA DLLEQIPDLG EDVKDPEDCF TEGCVRRCPC CMVDTTQSPG KVWWRLRKTC
YRIVEHSWFE TFIIFMILLS SGALAFEDIY LEERKTIKVL LEYADKMFTY VFVLEMLLKW
VAYGFKKYFT NAWCWLDFLI VDVSLVSLVA NTLGFAEMGP IKSLRTLRAL RPLRALSRFE
GMRVVVNALV GAIPSIMNVL LVCLIFWLIF SIMGVNLFAG KFGRCINQTE GDLPLNYTIV
NNKSECESFN VTGELYWTKV KVNFDNVGAG YLALLQVATF KGWMDIMYAA VDSRGYEEQP
QWEDNLYMYI YFVVFIIFGS FFTLNLFIGV IIDNFNQQKK KLGGQDIFMT EEQKKYYNAM
KKLGSKKPQK PIPRPLNKYQ GFIFDIVTKQ AFDVTIMFLI CLNMVTMMVE TDDQSPEKVN
ILAKINLLFV AIFTGECIVK MAALRHYYFT NSWNIFDFVV VILSIVGTVL SDIIQKYFFS
PTLFRVIRLA RIGRILRLIR GAKGIRTLLF ALMMSLPALF NIGLLLFLVM FIYSIFGMAN
FAYVKWEAGI DDMFNFQTFA NSMLCLFQIT TSAGWDGLLS PILNTGPPYC DPNLPNSNGS
RGNCGSPAVG ILFFTTYIII SFLIVVNMYI AIILENFSVA TEESTEPLSE DDFDMFYEIW
EKFDPEATQF IEYLALSDFA DALSEPLRIA KPNQISLINM DLPMVSGDRI HCMDILFAFT
KRVLGESGEM DALKIQMEEK FMAANPSKIS YEPITTTLRR KHEEVSATVI QRAFRRHLLQ
RSVKHASFLF RQQAGGSGLS DEDAPEREGL IAYMMNGNFS RRSAPLSSSS ISSTSFPPSY
DSVTRATSDN LPVRASDYSR SEDLADFPPS PDRDRESIV
