SCN5A_MOUSE
ID SCN5A_MOUSE Reviewed; 2019 AA.
AC Q9JJV9; E9Q1D2; Q3UH91;
DT 16-JUN-2009, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 152.
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;
DE AltName: Full=mH1;
GN Name=Scn5a;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION,
RP ALTERNATIVE SPLICING, AND TISSUE SPECIFICITY.
RC STRAIN=BALB/cJ; TISSUE=Heart;
RX PubMed=11834499; DOI=10.1152/ajpheart.00644.2001;
RA Zimmer T., Bollensdorff C., Haufe V., Birch-Hirschfeld E., Benndorf K.;
RT "Mouse heart Na+ channels: primary structure and function of two isoforms
RT and alternatively spliced variants.";
RL Am. J. Physiol. 282:H1007-H1017(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=C57BL/6J;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP INTERACTION WITH SNTA1; SNTB1 AND SNTB2.
RX PubMed=9412493; DOI=10.1523/jneurosci.18-01-00128.1998;
RA Gee S.H., Madhavan R., Levinson S.R., Caldwell J.H., Sealock R.,
RA Froehner S.C.;
RT "Interaction of muscle and brain sodium channels with multiple members of
RT the syntrophin family of dystrophin-associated proteins.";
RL J. Neurosci. 18:128-137(1998).
RN [5]
RP PHOSPHORYLATION BY CAMK2D.
RX PubMed=17124532; DOI=10.1172/jci26620;
RA Wagner S., Dybkova N., Rasenack E.C., Jacobshagen C., Fabritz L.,
RA Kirchhof P., Maier S.K., Zhang T., Hasenfuss G., Brown J.H., Bers D.M.,
RA Maier L.S.;
RT "Ca2+/calmodulin-dependent protein kinase II regulates cardiac Na+
RT channels.";
RL J. Clin. Invest. 116:3127-3138(2006).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-457; SER-484 AND SER-539, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Heart, and Liver;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [7]
RP INTERACTION WITH FGF13.
RX PubMed=21817159; DOI=10.1161/circresaha.111.247957;
RA Wang C., Hennessey J.A., Kirkton R.D., Wang C., Graham V., Puranam R.S.,
RA Rosenberg P.B., Bursac N., Pitt G.S.;
RT "Fibroblast growth factor homologous factor 13 regulates Na+ channels and
RT conduction velocity in murine hearts.";
RL Circ. Res. 109:775-782(2011).
RN [8]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=23420830; DOI=10.1161/circep.111.000206;
RA Chakrabarti S., Wu X., Yang Z., Wu L., Yong S.L., Zhang C., Hu K.,
RA Wang Q.K., Chen Q.;
RT "MOG1 rescues defective trafficking of Na(v)1.5 mutations in Brugada
RT syndrome and sick sinus syndrome.";
RL Circ. Arrhythm. Electrophysiol. 6:392-401(2013).
RN [9]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-526, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
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 (PubMed:11834499, PubMed:23420830). It is a tetrodotoxin-resistant
CC Na(+) channel isoform. This channel is responsible for the initial
CC upstroke of the action potential. Channel inactivation is regulated by
CC intracellular calcium levels (By similarity).
CC {ECO:0000250|UniProtKB:Q14524, ECO:0000269|PubMed:11834499,
CC ECO:0000269|PubMed:23420830}.
CC -!- SUBUNIT: Interacts with the PDZ domain of the syntrophin SNTA1, SNTB1
CC and SNTB2 (PubMed:9412493). Interacts with NEDD4, NEDD4L, WWP2 and
CC GPD1L (By similarity). Interacts with CALM (By similarity). Interacts
CC with FGF13; the interaction is direct and may regulate SNC5A density at
CC membranes and function (PubMed:21817159). Interacts with FGF12 and
CC FGF14 (By similarity). Interacts with ANK3 (By similarity).
CC {ECO:0000250|UniProtKB:Q14524, ECO:0000269|PubMed:21817159,
CC ECO:0000269|PubMed:9412493}.
CC -!- INTERACTION:
CC Q9JJV9; Q4U4S6: Xirp2; NbExp=2; IntAct=EBI-8313814, EBI-10768169;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:11834499,
CC ECO:0000269|PubMed:23420830}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:D0E0C2}. Cytoplasm, perinuclear region
CC {ECO:0000250|UniProtKB:Q14524}. Cell membrane, sarcolemma, T-tubule
CC {ECO:0000250|UniProtKB:P15389}. Note=RANGRF promotes trafficking to the
CC cell membrane. {ECO:0000269|PubMed:23420830}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Comment=Additional isoforms seem to exist.;
CC Name=1;
CC IsoId=Q9JJV9-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9JJV9-2; Sequence=VSP_037444;
CC -!- TISSUE SPECIFICITY: Expressed in the myocardium.
CC {ECO:0000269|PubMed:11834499}.
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 (By similarity). Regulated through phosphorylation
CC by CaMK2D (PubMed:17124532). {ECO:0000250|UniProtKB:Q14524,
CC ECO:0000269|PubMed:17124532}.
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 868) 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:0000250|UniProtKB:P15389}.
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; AJ271477; CAB70096.1; -; mRNA.
DR EMBL; AK147254; BAE27800.1; -; mRNA.
DR EMBL; AK147517; BAE27966.1; -; mRNA.
DR EMBL; AC121922; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC171201; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; NP_001240789.1; NM_001253860.1.
DR RefSeq; NP_067519.2; NM_021544.4.
DR AlphaFoldDB; Q9JJV9; -.
DR BMRB; Q9JJV9; -.
DR SMR; Q9JJV9; -.
DR BioGRID; 203101; 14.
DR DIP; DIP-46142N; -.
DR IntAct; Q9JJV9; 4.
DR MINT; Q9JJV9; -.
DR STRING; 10090.ENSMUSP00000112838; -.
DR BindingDB; Q9JJV9; -.
DR ChEMBL; CHEMBL4630764; -.
DR GlyGen; Q9JJV9; 13 sites.
DR iPTMnet; Q9JJV9; -.
DR PhosphoSitePlus; Q9JJV9; -.
DR CPTAC; non-CPTAC-4004; -.
DR PaxDb; Q9JJV9; -.
DR PRIDE; Q9JJV9; -.
DR ProteomicsDB; 253414; -. [Q9JJV9-1]
DR ProteomicsDB; 253415; -. [Q9JJV9-2]
DR ABCD; Q9JJV9; 2 sequenced antibodies.
DR Antibodypedia; 6411; 319 antibodies from 32 providers.
DR DNASU; 20271; -.
DR Ensembl; ENSMUST00000120420; ENSMUSP00000113272; ENSMUSG00000032511. [Q9JJV9-1]
DR GeneID; 20271; -.
DR KEGG; mmu:20271; -.
DR UCSC; uc009sbc.2; mouse. [Q9JJV9-2]
DR CTD; 6331; -.
DR MGI; MGI:98251; Scn5a.
DR VEuPathDB; HostDB:ENSMUSG00000032511; -.
DR eggNOG; KOG2301; Eukaryota.
DR GeneTree; ENSGT00940000161691; -.
DR InParanoid; Q9JJV9; -.
DR OrthoDB; 172471at2759; -.
DR TreeFam; TF323985; -.
DR Reactome; R-MMU-5576892; Phase 0 - rapid depolarisation.
DR BioGRID-ORCS; 20271; 2 hits in 73 CRISPR screens.
DR PRO; PR:Q9JJV9; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; Q9JJV9; protein.
DR Bgee; ENSMUSG00000032511; Expressed in myocardium of ventricle and 114 other tissues.
DR ExpressionAtlas; Q9JJV9; baseline and differential.
DR Genevisible; Q9JJV9; MM.
DR GO; GO:0005901; C:caveola; ISO:MGI.
DR GO; GO:0009986; C:cell surface; IDA:BHF-UCL.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:MGI.
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; IDA:BHF-UCL.
DR GO; GO:0005730; C:nucleolus; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IDA:MGI.
DR GO; GO:0042383; C:sarcolemma; ISO:MGI.
DR GO; GO:0034706; C:sodium channel complex; IPI:MGI.
DR GO; GO:0030315; C:T-tubule; IDA:MGI.
DR GO; GO:0001518; C:voltage-gated sodium channel complex; ISO:MGI.
DR GO; GO:0030018; C:Z disc; ISO:MGI.
DR GO; GO:0030506; F:ankyrin binding; ISO:MGI.
DR GO; GO:0005516; F:calmodulin binding; ISO:MGI.
DR GO; GO:0019899; F:enzyme binding; ISO:MGI.
DR GO; GO:0017134; F:fibroblast growth factor binding; ISO:MGI.
DR GO; GO:0050998; F:nitric-oxide synthase binding; ISO:MGI.
DR GO; GO:0019904; F:protein domain specific binding; ISO:MGI.
DR GO; GO:0019901; F:protein kinase binding; ISO:MGI.
DR GO; GO:0097110; F:scaffold protein binding; IPI:BHF-UCL.
DR GO; GO:0044325; F:transmembrane transporter binding; ISO:MGI.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:MGI.
DR GO; GO:0005244; F:voltage-gated ion channel activity; IEA:UniProtKB-KW.
DR GO; GO:0005248; F:voltage-gated sodium channel activity; ISO:MGI.
DR GO; GO:0086060; F:voltage-gated sodium channel activity involved in AV node cell action potential; ISO:MGI.
DR GO; GO:0086061; F:voltage-gated sodium channel activity involved in bundle of His cell action potential; ISO:MGI.
DR GO; GO:0086006; F:voltage-gated sodium channel activity involved in cardiac muscle cell action potential; IMP:MGI.
DR GO; GO:0086062; F:voltage-gated sodium channel activity involved in Purkinje myocyte action potential; ISO:MGI.
DR GO; GO:0086063; F:voltage-gated sodium channel activity involved in SA node cell action potential; IMP:MGI.
DR GO; GO:0086014; P:atrial cardiac muscle cell action potential; ISO:MGI.
DR GO; GO:0086016; P:AV node cell action potential; ISO:MGI.
DR GO; GO:0086067; P:AV node cell to bundle of His cell communication; ISO:MGI.
DR GO; GO:0086043; P:bundle of His cell action potential; ISO:MGI.
DR GO; GO:0086002; P:cardiac muscle cell action potential involved in contraction; ISO:MGI.
DR GO; GO:0060048; P:cardiac muscle contraction; ISO:MGI.
DR GO; GO:0003231; P:cardiac ventricle development; IMP:MGI.
DR GO; GO:0071277; P:cellular response to calcium ion; ISS:UniProtKB.
DR GO; GO:0051899; P:membrane depolarization; ISO:MGI.
DR GO; GO:0086010; P:membrane depolarization during action potential; ISO:MGI.
DR GO; GO:0098912; P:membrane depolarization during atrial cardiac muscle cell action potential; ISO:MGI.
DR GO; GO:0086045; P:membrane depolarization during AV node cell action potential; ISO:MGI.
DR GO; GO:0086048; P:membrane depolarization during bundle of His cell action potential; ISO:MGI.
DR GO; GO:0086012; P:membrane depolarization during cardiac muscle cell action potential; ISO:MGI.
DR GO; GO:0086047; P:membrane depolarization during Purkinje myocyte cell action potential; ISO:MGI.
DR GO; GO:0086046; P:membrane depolarization during SA node cell action potential; ISO:MGI.
DR GO; GO:0019228; P:neuronal action potential; IBA:GO_Central.
DR GO; GO:0045760; P:positive regulation of action potential; ISO:MGI.
DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; ISO:MGI.
DR GO; GO:0010460; P:positive regulation of heart rate; ISO:MGI.
DR GO; GO:0010765; P:positive regulation of sodium ion transport; ISO:MGI.
DR GO; GO:0060371; P:regulation of atrial cardiac muscle cell membrane depolarization; ISO:MGI.
DR GO; GO:0060372; P:regulation of atrial cardiac muscle cell membrane repolarization; ISO:MGI.
DR GO; GO:0086004; P:regulation of cardiac muscle cell contraction; IMP:MGI.
DR GO; GO:0002027; P:regulation of heart rate; ISO:MGI.
DR GO; GO:0086091; P:regulation of heart rate by cardiac conduction; IMP:MGI.
DR GO; GO:1902305; P:regulation of sodium ion transmembrane transport; ISO:MGI.
DR GO; GO:0060373; P:regulation of ventricular cardiac muscle cell membrane depolarization; ISO:MGI.
DR GO; GO:0060307; P:regulation of ventricular cardiac muscle cell membrane repolarization; ISO:MGI.
DR GO; GO:0014894; P:response to denervation involved in regulation of muscle adaptation; ISO:MGI.
DR GO; GO:0014070; P:response to organic cyclic compound; IMP:MGI.
DR GO; GO:0086015; P:SA node cell action potential; ISO:MGI.
DR GO; GO:0098719; P:sodium ion import across plasma membrane; ISO:MGI.
DR GO; GO:0035725; P:sodium ion transmembrane transport; ISO:MGI.
DR GO; GO:0006814; P:sodium ion transport; ISO:MGI.
DR GO; GO:0086005; P:ventricular cardiac muscle cell action potential; ISO:MGI.
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 Alternative splicing; Calmodulin-binding; Cell membrane; Cytoplasm;
KW Disulfide bond; Glycoprotein; Ion channel; Ion transport; Membrane;
KW 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_0000376895"
FT TOPO_DOM 1..131
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 132..150
FT /note="Helical; Name=S1 of repeat I"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 151..157
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 158..178
FT /note="Helical; Name=S2 of repeat I"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 179..192
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 193..210
FT /note="Helical; Name=S3 of repeat I"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 211..216
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 217..233
FT /note="Helical; Name=S4 of repeat I"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 234..252
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 253..272
FT /note="Helical; Name=S5 of repeat I"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 273..357
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT INTRAMEM 358..382
FT /note="Pore-forming"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 383..389
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 390..410
FT /note="Helical; Name=S6 of repeat I"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 411..717
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 718..736
FT /note="Helical; Name=S1 of repeat II"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 737..747
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 748..767
FT /note="Helical; Name=S2 of repeat II"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 768..781
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 782..801
FT /note="Helical; Name=S3 of repeat II"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 802..803
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 804..821
FT /note="Helical; Name=S4 of repeat II"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 822..837
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 838..856
FT /note="Helical; Name=S5 of repeat II"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 857..885
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT INTRAMEM 886..906
FT /note="Pore-forming"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 907..919
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 920..940
FT /note="Helical; Name=S6 of repeat II"
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT TOPO_DOM 941..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 113..420
FT /note="I"
FT /evidence="ECO:0000305"
FT REPEAT 699..971
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..68
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 461..575
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 610..647
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1000..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 1963..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 480..500
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 503..526
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1020..1039
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1056..1071
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1096..1118
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1963..1995
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 36
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14524"
FT MOD_RES 38
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q14524"
FT MOD_RES 457
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 460
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14524"
FT MOD_RES 483
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14524"
FT MOD_RES 484
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 486
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P15389"
FT MOD_RES 497
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14524"
FT MOD_RES 510
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14524"
FT MOD_RES 526
FT /note="Dimethylated arginine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q14524"
FT MOD_RES 526
FT /note="Omega-N-methylarginine; alternate"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 539
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 571
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14524"
FT MOD_RES 664
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q14524"
FT MOD_RES 667
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 214
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 283
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 288
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 291
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 318
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 328
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 740
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 803
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 864
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 280..335
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT DISULFID 908..917
FT /evidence="ECO:0000250|UniProtKB:D0E0C2"
FT VAR_SEQ 206..211
FT /note="TTEFVD -> VSENIK (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_037444"
FT CONFLICT 215
FT /note="V -> L (in Ref. 2; BAE27966/BAE27800)"
FT /evidence="ECO:0000305"
FT CONFLICT 234
FT /note="S -> P (in Ref. 2; BAE27966/BAE27800)"
FT /evidence="ECO:0000305"
FT CONFLICT 1008..1009
FT /note="AA -> TT (in Ref. 1; CAB70096)"
FT /evidence="ECO:0000305"
FT CONFLICT 1078
FT /note="K -> KQ (in Ref. 2; BAE27966/BAE27800)"
FT /evidence="ECO:0000305"
FT CONFLICT 1133
FT /note="T -> S (in Ref. 1; CAB70096)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 2019 AA; 227576 MW; 5A3BC3C191859E79 CRC64;
MANFLLPRGT SSFRRFTRES LAAIEKRMAE KQARGSATSQ ESREGLPEEE APRPQLDLQA
SKKLPDLYGN PPRELIGEPL EDLDPFYSTQ KTFIVLNKGK TIFRFSATNA LYVLSPFHPV
RRAAVKILVH SLFSMLIMCT ILTNCVFMAQ HDPPPWTKYV EYTFTAIYTF ESLVKILARG
FCLHAFTFLR DPWNWLDFSV IVMAYTTEFV DLGNVSALRT FRVLRALKTI SVISGLKTIV
GALIQSVKKL ADVMVLTVFC LSVFALIGLQ LFMGNLRHKC VRNFTELNGT NGSVEADGIV
WNSLDVYLND PANYLLKNGT TDVLLCGNSS DAGTCPEGYR CLKAGENPDH GYTSFDSFAW
AFLALFRLMT QDCWERLYQQ TLRSAGKIYM IFFMLVIFLG SFYLVNLILA VVAMAYEEQN
QATIAETEEK EKRFQEAMEM LKKEHEALTI RGVDTVSRSS LEMSPLAPVT NHERRSKRRK
RLSSGTEDGG DDRLPKSDSE DGPRALNQLS LTHGLSRTSM RPRSSRGSIF TFRRRDQGSE
ADFADDENST AGESESHRTS LLVPWPLRRP STQGQPGFGT SAPGHVLNGK RNSTVDCNGV
VSLLGAGDAE ATSPGSHLLR PIVLDRPPDT TTPSEEPGGP QMLTPQAPCA DGFEEPGARQ
RALSAVSVLT SALEELEESH RKCPPCWNRF AQHYLIWECC PLWMSIKQKV KFVVMDPFAD
LTITMCIVLN TLFMALEHYN MTAEFEEMLQ VGNLVFTGIF TAEMTFKIIA LDPYYYFQQG
WNIFDSIIVI LSLMELGLSR MGNLSVLRSF RLLRVFKLAK SWPTLNTLIK IIGNSVGALG
NLTLVLAIIV FIFAVVGMQL FGKNYSELRH RISDSGLLPR WHMMDFFHAF LIIFRILCGE
WIETMWDCME VSGQSLCLLV FLLVMVIGNL VVLNLFLALL LSSFSADNLT APDEDGEMNN
LQLALARIQR GLRFVKRTTW DFCCGLLRRR PKKPAALATH SQLPSCIAAP RSPPPPEVEK
APPARKETRF EEDKRPGQGT PGDTEPVCVP IAVAESDTDD QEEDEENSLG TEEEESSKQE
SQVVSGGHEP PQEPRAWSQV SETTSSEAEA STSQADWQQE REAEPRAPGC GETPEDSYSE
GSTADMTNTA DLLEQIPDLG EDVKDPEDCF TEGCVRRCPC CMVDTTQAPG 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 RQQAGSSGLS DEDAPEREGL IAYMMNENFS RRSGPLSSSS ISSTSFPPSY
DSVTRATSDN LPVRASDYSR SEDLADFPPS PDRDRESIV
