NALCN_MOUSE
ID NALCN_MOUSE Reviewed; 1738 AA.
AC Q8BXR5; Q8BYM2;
DT 15-JAN-2008, integrated into UniProtKB/Swiss-Prot.
DT 15-JAN-2008, sequence version 2.
DT 03-AUG-2022, entry version 141.
DE RecName: Full=Sodium leak channel NALCN {ECO:0000305};
DE AltName: Full=Sodium leak channel non-selective protein;
DE AltName: Full=Voltage gated channel-like protein 1;
GN Name=Nalcn; Synonyms=Vgcnl1;
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 [LARGE SCALE MRNA] (ISOFORM 2), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 1229-1738 (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Hypothalamus, and Retina;
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 [2]
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 [3]
RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=17448995; DOI=10.1016/j.cell.2007.02.041;
RA Lu B., Su Y., Das S., Liu J., Xia J., Ren D.;
RT "The neuronal channel NALCN contributes resting sodium permeability and is
RT required for normal respiratory rhythm.";
RL Cell 129:371-383(2007).
RN [4]
RP FUNCTION, PHOSPHORYLATION, AND INTERACTION WITH UNC80.
RX PubMed=19092807; DOI=10.1038/nature07579;
RA Lu B., Su Y., Das S., Wang H., Wang Y., Liu J., Ren D.;
RT "Peptide neurotransmitters activate a cation channel complex of NALCN and
RT UNC-80.";
RL Nature 457:741-744(2009).
RN [5]
RP FUNCTION, TISSUE SPECIFICITY, AND INTERACTION WITH CHRM3.
RX PubMed=19575010; DOI=10.1038/embor.2009.125;
RA Swayne L.A., Mezghrani A., Varrault A., Chemin J., Bertrand G., Dalle S.,
RA Bourinet E., Lory P., Miller R.J., Nargeot J., Monteil A.;
RT "The NALCN ion channel is activated by M3 muscarinic receptors in a
RT pancreatic beta-cell line.";
RL EMBO Rep. 10:873-880(2009).
RN [6]
RP SUBUNIT, AND FUNCTION.
RX PubMed=21040849; DOI=10.1016/j.neuron.2010.09.014;
RA Lu B., Zhang Q., Wang H., Wang Y., Nakayama M., Ren D.;
RT "Extracellular calcium controls background current and neuronal
RT excitability via an UNC79-UNC80-NALCN cation channel complex.";
RL Neuron 68:488-499(2010).
RN [7]
RP FUNCTION.
RX PubMed=21177381; DOI=10.1152/physiolgenomics.00188.2010;
RA Sinke A.P., Caputo C., Tsaih S.W., Yuan R., Ren D., Deen P.M.,
RA Korstanje R.;
RT "Genetic analysis of mouse strains with variable serum sodium
RT concentrations identifies the Nalcn sodium channel as a novel player in
RT osmoregulation.";
RL Physiol. Genomics 43:265-270(2011).
RN [8]
RP FUNCTION.
RX PubMed=22508057; DOI=10.1159/000338504;
RA Kim B.J., Chang I.Y., Choi S., Jun J.Y., Jeon J.H., Xu W.X., Kwon Y.K.,
RA Ren D., So I.;
RT "Involvement of Na(+)-leak channel in substance P-induced depolarization of
RT pacemaking activity in interstitial cells of Cajal.";
RL Cell. Physiol. Biochem. 29:501-510(2012).
RN [9]
RP FUNCTION.
RX PubMed=27177420; DOI=10.7554/elife.15271;
RA Lutas A., Lahmann C., Soumillon M., Yellen G.;
RT "The leak channel NALCN controls tonic firing and glycolytic sensitivity of
RT substantia nigra pars reticulata neurons.";
RL Elife 5:0-0(2016).
CC -!- FUNCTION: Voltage-gated ion channel responsible for the resting Na(+)
CC permeability that controls neuronal excitability. NALCN channel
CC functions as a multi-protein complex, which consists at least of NALCN,
CC NALF1, UNC79 and UNC80. NALCN is the voltage-sensing, pore-forming
CC subunit of the NALCN channel complex. NALCN channel complex is
CC constitutively active and conducts monovalent cations but is blocked by
CC physiological concentrations of extracellular divalent cations (By
CC similarity). In addition to its role in regulating neuronal
CC excitability, is required for normal respiratory rhythm, systemic
CC osmoregulation by controlling the serum sodium concentration and in the
CC regulation of the intestinal pace-making activity in the interstitial
CC cells of Cajal (PubMed:21177381, PubMed:22508057). Plays a critical
CC role in both maintenance of spontaneous firing of substantia nigra pars
CC reticulata (SNr) neurons and physiological modulation of SNr neuron
CC excitability (PubMed:27177420). NALCN channel is also activated by
CC neuropeptides such as neurotensin and substance P (SP) through a SRC
CC family kinases-dependent pathway (PubMed:19092807). In addition, NALCN
CC activity is enhanced/modulated by several GPCRs, such as CHRM3
CC (PubMed:19092807, PubMed:19575010, PubMed:21040849).
CC {ECO:0000250|UniProtKB:Q8IZF0, ECO:0000269|PubMed:19092807,
CC ECO:0000269|PubMed:19575010, ECO:0000269|PubMed:21040849,
CC ECO:0000269|PubMed:21177381, ECO:0000269|PubMed:22508057,
CC ECO:0000269|PubMed:27177420}.
CC -!- ACTIVITY REGULATION: Inhibited by low micromolar concentrations of
CC Gd(3+) and high micromolar concentrations of verapamil. Insensitive to
CC tetrodotoxin (TTX) and potentiated by low external Ca(2+)
CC concentration. {ECO:0000250|UniProtKB:Q8IZF0}.
CC -!- SUBUNIT: Found in a complex with NALCN, UNC79, UNC80 and NACL1; these
CC auxiliary subunits are indispensable for the function of the NALCN
CC channel (By similarity). Interacts with UNC80; required for the NALCN
CC activation/inhibition by GPCRs in neurons (PubMed:19092807,
CC PubMed:21040849). Found in a complex with NALCN, UNC79 and UNC80; UNC80
CC bridges NALCN to UNC79 (PubMed:21040849). Interacts with CHRM3
CC (PubMed:19575010). {ECO:0000250|UniProtKB:Q8IZF0,
CC ECO:0000269|PubMed:19092807, ECO:0000269|PubMed:19575010,
CC ECO:0000269|PubMed:21040849}.
CC -!- INTERACTION:
CC Q8BXR5; B8XCJ6: Unc80; NbExp=2; IntAct=EBI-11570410, EBI-15747640;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q8IZF0};
CC Multi-pass membrane protein {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8BXR5-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8BXR5-2; Sequence=VSP_030192;
CC -!- TISSUE SPECIFICITY: Widely expressed in the brain and spinal cord
CC neurons (PubMed:17448995). Expressed also in pancreatic islet cells
CC (PubMed:19575010). {ECO:0000269|PubMed:17448995,
CC ECO:0000269|PubMed:19575010}.
CC -!- DOMAIN: Contains 24 transmembrane helices (TM) that form four
CC homologous functional repeats connected by intracellular linkers. Each
CC of the four internal repeats contains five hydrophobic transmembrane
CC segments (S1, S2, S3, S5, S6) and one positively charged transmembrane
CC segment (S4). S4 segments represent the voltage-sensor. S4
CC transmembrane segments lack some of the charged residues (K and R)
CC found at every third position in the S4s of the NaV, CaV, and KV
CC channels. Pore-forming loops (P loops) between S5 and S6 of each domain
CC form an EEKE sodium- ion selectivity filter a mixture between the EEEE
CC found in the CaVs and the DEKA of NaVs. Voltage-sensing domains (VSDs),
CC formed by S1 to S4 of each domain, detect changes in membrane potential
CC and induce the opening or closing of the ion-conducting pore domain,
CC formed by S5 and S6.
CC -!- PTM: Phosphorylated on tyrosine residues.
CC {ECO:0000269|PubMed:19092807}.
CC -!- DISRUPTION PHENOTYPE: Deficient mice exhibit abnormal breathing at
CC birth and die within 24 hours. {ECO:0000269|PubMed:17448995}.
CC -!- SIMILARITY: Belongs to the NALCN family. {ECO:0000305}.
CC -!- CAUTION: NALCN was also originally reported to be a voltage-
CC independent, cation-nonselective channel which is permeable to sodium,
CC potassium and calcium ions (PubMed:17448995). However, NALCN is
CC recently reported to be selective only for monovalent cations and to be
CC blocked by extracellular divalent cations (By similarity). Futhemore,
CC coexpression of NALCN, UNC79, UNC80, and NALF1 results in voltage-
CC dependent NALCN currents (By similarity).
CC {ECO:0000250|UniProtKB:Q8IZF0, ECO:0000269|PubMed:17448995}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC31915.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AK039034; BAC30213.1; -; mRNA.
DR EMBL; AK044431; BAC31915.1; ALT_FRAME; mRNA.
DR EMBL; AC102783; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC154677; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC124818; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; NP_796367.3; NM_177393.4.
DR AlphaFoldDB; Q8BXR5; -.
DR SMR; Q8BXR5; -.
DR BioGRID; 237222; 8.
DR DIP; DIP-59731N; -.
DR IntAct; Q8BXR5; 2.
DR STRING; 10090.ENSMUSP00000000201; -.
DR iPTMnet; Q8BXR5; -.
DR PhosphoSitePlus; Q8BXR5; -.
DR PaxDb; Q8BXR5; -.
DR PRIDE; Q8BXR5; -.
DR ProteomicsDB; 293619; -. [Q8BXR5-1]
DR ABCD; Q8BXR5; 1 sequenced antibody.
DR DNASU; 338370; -.
DR GeneID; 338370; -.
DR KEGG; mmu:338370; -.
DR UCSC; uc007vbr.1; mouse. [Q8BXR5-1]
DR UCSC; uc007vbs.1; mouse. [Q8BXR5-2]
DR CTD; 259232; -.
DR MGI; MGI:2444306; Nalcn.
DR eggNOG; KOG2301; Eukaryota.
DR InParanoid; Q8BXR5; -.
DR OrthoDB; 172471at2759; -.
DR PhylomeDB; Q8BXR5; -.
DR Reactome; R-MMU-2672351; Stimuli-sensing channels.
DR BioGRID-ORCS; 338370; 2 hits in 72 CRISPR screens.
DR PRO; PR:Q8BXR5; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q8BXR5; protein.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0005261; F:cation channel activity; IDA:UniProtKB.
DR GO; GO:0022840; F:leak channel activity; IMP:UniProtKB.
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:0070588; P:calcium ion transmembrane transport; IDA:UniProtKB.
DR GO; GO:0032224; P:positive regulation of synaptic transmission, cholinergic; IBA:GO_Central.
DR GO; GO:0032230; P:positive regulation of synaptic transmission, GABAergic; IBA:GO_Central.
DR GO; GO:0071805; P:potassium ion transmembrane transport; IDA:UniProtKB.
DR GO; GO:0034765; P:regulation of ion transmembrane transport; IEA:UniProtKB-KW.
DR GO; GO:0060075; P:regulation of resting membrane potential; IMP:UniProtKB.
DR GO; GO:0035725; P:sodium ion transmembrane transport; IDA:UniProtKB.
DR Gene3D; 1.20.120.350; -; 4.
DR InterPro; IPR005821; Ion_trans_dom.
DR InterPro; IPR028823; NALCN.
DR InterPro; IPR027359; Volt_channel_dom_sf.
DR PANTHER; PTHR46141; PTHR46141; 1.
DR Pfam; PF00520; Ion_trans; 4.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Coiled coil; Disulfide bond;
KW Glycoprotein; Ion channel; Ion transport; Membrane; Phosphoprotein;
KW Reference proteome; Repeat; Sodium; Sodium channel; Sodium transport;
KW Transmembrane; Transmembrane helix; Transport; Voltage-gated channel.
FT CHAIN 1..1738
FT /note="Sodium leak channel NALCN"
FT /id="PRO_0000314011"
FT TOPO_DOM 1..36
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q8IZF0"
FT TRANSMEM 37..57
FT /note="Helical; Name=S1 of repeat I"
FT /evidence="ECO:0000250|UniProtKB:Q8IZF0"
FT TOPO_DOM 58..65
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q8IZF0"
FT TRANSMEM 66..90
FT /note="Helical; Name=S2 of repeat I"
FT /evidence="ECO:0000250|UniProtKB:Q8IZF0"
FT TOPO_DOM 91..106
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q8IZF0"
FT TRANSMEM 107..129
FT /note="Helical; Name=S3 of repeat I"
FT /evidence="ECO:0000250|UniProtKB:Q8IZF0"
FT TOPO_DOM 130..137
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q8IZF0"
FT TRANSMEM 138..158
FT /note="Helical; Voltage-sensor; Name=S4 of repeat I"
FT /evidence="ECO:0000250|UniProtKB:Q8IZF0"
FT TOPO_DOM 159..173
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q8IZF0"
FT TRANSMEM 174..199
FT /note="Helical; Name=S5 of repeat I"
FT /evidence="ECO:0000250|UniProtKB:Q8IZF0"
FT TOPO_DOM 200..269
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q8IZF0"
FT INTRAMEM 270..289
FT /note="Pore-forming"
FT /evidence="ECO:0000250|UniProtKB:Q8IZF0"
FT TOPO_DOM 290..294
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q8IZF0"
FT TRANSMEM 295..322
FT /note="Helical; Name=S6 of repeat I"
FT /evidence="ECO:0000250|UniProtKB:Q8IZF0"
FT TOPO_DOM 323..382
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q8IZF0"
FT TRANSMEM 383..403
FT /note="Helical; Name=S1 of repeat II"
FT /evidence="ECO:0000250|UniProtKB:Q8IZF0"
FT TOPO_DOM 404..416
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q8IZF0"
FT TRANSMEM 417..439
FT /note="Helical; Name=S2 of repeat II"
FT /evidence="ECO:0000250|UniProtKB:Q8IZF0"
FT TOPO_DOM 440..447
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q8IZF0"
FT TRANSMEM 448..468
FT /note="Helical; Name=S3 of repeat II"
FT /evidence="ECO:0000250|UniProtKB:Q8IZF0"
FT TOPO_DOM 469..472
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q8IZF0"
FT TRANSMEM 473..492
FT /note="Helical; Voltage-sensor; Name=S4 of repeat II"
FT /evidence="ECO:0000250|UniProtKB:Q8IZF0"
FT TOPO_DOM 493..502
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q8IZF0"
FT TRANSMEM 503..530
FT /note="Helical; Name=S5 of repeat II"
FT /evidence="ECO:0000250|UniProtKB:Q8IZF0"
FT TOPO_DOM 531..543
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q8IZF0"
FT INTRAMEM 544..563
FT /note="Pore-forming"
FT /evidence="ECO:0000250|UniProtKB:Q8IZF0"
FT TOPO_DOM 564..578
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q8IZF0"
FT TRANSMEM 579..599
FT /note="Helical; Name=S6 of repeat II"
FT /evidence="ECO:0000250|UniProtKB:Q8IZF0"
FT TOPO_DOM 600..886
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q8IZF0"
FT TRANSMEM 887..906
FT /note="Helical; Name=S1 of repeat III"
FT /evidence="ECO:0000250|UniProtKB:Q8IZF0"
FT TOPO_DOM 907..915
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q8IZF0"
FT TRANSMEM 916..939
FT /note="Helical; Name=S2 of repeat III"
FT /evidence="ECO:0000250|UniProtKB:Q8IZF0"
FT TOPO_DOM 940..947
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q8IZF0"
FT TRANSMEM 948..972
FT /note="Helical; Name=S3 of repeat III"
FT /evidence="ECO:0000250|UniProtKB:Q8IZF0"
FT TOPO_DOM 973..980
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q8IZF0"
FT TRANSMEM 981..1003
FT /note="Helical; Voltage-sensor; Name=S4 of repeat III"
FT /evidence="ECO:0000250|UniProtKB:Q8IZF0"
FT TOPO_DOM 1004..1015
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q8IZF0"
FT TRANSMEM 1016..1039
FT /note="Helical; Name=S5 of repeat III"
FT /evidence="ECO:0000250|UniProtKB:Q8IZF0"
FT TOPO_DOM 1040..1104
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q8IZF0"
FT INTRAMEM 1105..1124
FT /note="Pore-forming"
FT /evidence="ECO:0000250|UniProtKB:Q8IZF0"
FT TOPO_DOM 1125..1129
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q8IZF0"
FT TRANSMEM 1130..1159
FT /note="Helical; Name=S6 of repeat III"
FT /evidence="ECO:0000250|UniProtKB:Q8IZF0"
FT TOPO_DOM 1160..1210
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q8IZF0"
FT TRANSMEM 1211..1227
FT /note="Helical; Name=S1 of repeat IV"
FT /evidence="ECO:0000250|UniProtKB:Q8IZF0"
FT TOPO_DOM 1228..1236
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q8IZF0"
FT TRANSMEM 1237..1260
FT /note="Helical; Name=S2 of repeat IV"
FT /evidence="ECO:0000250|UniProtKB:Q8IZF0"
FT TOPO_DOM 1261..1271
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q8IZF0"
FT TRANSMEM 1272..1293
FT /note="Helical; Name=S3 of repeat IV"
FT /evidence="ECO:0000250|UniProtKB:Q8IZF0"
FT TOPO_DOM 1294..1296
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q8IZF0"
FT TRANSMEM 1297..1318
FT /note="Helical; Voltage-sensor; Name=S4 of repeat IV"
FT /evidence="ECO:0000250|UniProtKB:Q8IZF0"
FT TOPO_DOM 1319..1331
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q8IZF0"
FT TRANSMEM 1332..1357
FT /note="Helical; Name=S5 of repeat IV"
FT /evidence="ECO:0000250|UniProtKB:Q8IZF0"
FT TOPO_DOM 1358..1378
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q8IZF0"
FT INTRAMEM 1379..1398
FT /note="Pore-forming"
FT /evidence="ECO:0000250|UniProtKB:Q8IZF0"
FT TOPO_DOM 1399..1420
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q8IZF0"
FT TRANSMEM 1421..1447
FT /note="Helical; Name=S6 of repeat IV"
FT /evidence="ECO:0000250|UniProtKB:Q8IZF0"
FT TOPO_DOM 1448..1738
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q8IZF0"
FT REGION 762..785
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1602..1679
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 795..830
FT /evidence="ECO:0000255"
FT COMPBIAS 1606..1653
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 210
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250|UniProtKB:Q8IZF0"
FT CARBOHYD 216
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250|UniProtKB:Q8IZF0"
FT CARBOHYD 1064
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250|UniProtKB:Q8IZF0"
FT DISULFID 207..239
FT /evidence="ECO:0000250|UniProtKB:Q8IZF0"
FT DISULFID 229..245
FT /evidence="ECO:0000250|UniProtKB:Q8IZF0"
FT DISULFID 1046..1057
FT /evidence="ECO:0000250|UniProtKB:Q8IZF0"
FT DISULFID 1405..1417
FT /evidence="ECO:0000250|UniProtKB:Q8IZF0"
FT VAR_SEQ 216..1738
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_030192"
FT CONFLICT 1229
FT /note="V -> F (in Ref. 1; BAC31915)"
FT /evidence="ECO:0000305"
FT CONFLICT 1607
FT /note="R -> RL (in Ref. 1; BAC31915)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1738 AA; 200441 MW; C35A414B4B694299 CRC64;
MLKRKQSSRV EAQPVTDFGP DESLSDNADI LWINKPWVHS LLRICAIISV ISVCMNTPMT
FEHYPPLQYV TFTLDTLLMF LYTAEMIAKM HIRGIVKGDS SYVKDRWCVF DGFMVFCLWV
SLVLQVFEIA DIVDQMSPWG MLRIPRPLIM IRAFRIYFRF ELPRTRITNI LKRSGEQIWS
VSIFLLFFLL LYGILGVQMF GTFTYHCVVN DTKPGNVTWN SLAIPDTHCS PELEEGYQCP
PGFKCMDLED LGLSRQELGY SGFNEIGTSI FTVYEASSQE GWVFLMYRAI DSFPRWRSYF
YFITLIFFLA WLVKNVFIAV IIETFAEIRV QFQQMWGTRS STTSTATTQM FHEDAAGGWQ
LVAVDVNKPQ GRAPACLQKM MRSSVFHMFI LSMVTVDVIV AASNYYKGEN FRRQYDEFYL
AEVAFTVLFD LEALLKIWCL GFTGYISSSL HKFELLLVIG TTLHVYPDLY HSQFTYFQVL
RVVRLIKISP ALEDFVYKIF GPGKKLGSLV VFTASLLIVM SAISLQMFCF VEELDRFTTF
PRAFMSMFQI LTQEGWVDVM DQTLNAVGHM WAPLVAIYFI LYHLFATLIL LSLFVAVILD
NLELDEDLKK LKQLKQSEAN ADTKEKLPLR LRIFEKFPNR PQMVKISKLP SDFTVPKIRE
SFMKQFIDRQ QQDTCCLFRI LPSTSSSSCD NPKKPTAEDN KYIDQKLRKS VFSIRARNLL
EKETAVTKIL RACTRQRMLS GSFEGQPAKE RSILSVQHHI RQERRSLRHG SNSQRISRGK
SLETLTQDHS NTVRYRNAQR EDSEIKMIQE KKEQAEMKRK VQEEELRENH PYFDKPLFIV
GREHRFRNFC RVVVRARFNA SKTDPVTGAV KNTKYHQLYD LLGLVTYLDW VMITVTICSC
ISMMFESPFR RVMHAPTLQI AEYVFVIFMS IELNLKIMAD GLFFTPTAVI RDFGGVMDIF
IYLVSLIFLC WMPQNVPAES GAQLLMVLRC LRPLRIFKLV PQMRKVVREL FSGFKEIFLV
SILLLTLMLV FASFGVQLFA GKLAKCNDPN IIRREDCNGI FRINVSVSKN LNLKLRPGEK
KPGFWVPRVW ANPRNFNFDN VGNAMLALFE VLSLKGWVEV RDVIIHRVGP IHGIYIHVFV
FLGCMIGLTL FVGVVIANFN ENKGTALLTV DQRRWEDLKS RLKIAQPLHL PPRPDNDGFR
AKMYDITQHP FFKRTIALLV LAQSVLLSVK WDVDDPVTVP LATMSVVFTF IFVLEVTMKI
IAMSPAGFWQ SRRNRYDLLV TSLGVVWVVL HFALLNAYTY MMGACVIVFR FFSICGKHVT
LKMLLLTVVV SMYKSFFIIV GMFLLLLCYA FAGVVLFGTV KYGENINRHA NFSSAGKAIT
VLFRIVTGED WNKIMHDCMV QPPFCTPDEF TYWATDCGNY AGALMYFCSF YVIIAYIMLN
LLVAIIVENF SLFYSTEEDQ LLSYNDLRHF QIIWNMVDDK REGVIPTFRV KFLLRLLRGR
LEVDLDKDKL LFKHMCYEME RLHNGGDVTF HDVLSMLSYR SVDIRKSLQL EELLAREQLE
YTIEEEVAKQ TIRMWLKKCL KRIRAKQQQS CSIIHSLRES QEQERSRFLN PPSIETTQPS
EDSNANSQDH SMQPETSSQQ QLLSPTLSDR GGSRQDAADT GKPQRKIGQW RLPSAPKPIS
HSVSSVNLRF GGRTTMKTVV CKMNPMPDTA SCGSEVKKWW TRQLTVESDE SGDDLLDI
