ID SCN7A_HUMAN Reviewed; 1682 AA. AC Q01118; DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot. DT 18-MAY-2010, sequence version 2. DT 27-MAR-2024, entry version 203. DE RecName: Full=Sodium channel protein type 7 subunit alpha {ECO:0000305}; DE AltName: Full=Atypical sodium channel Nav2.1 {ECO:0000303|PubMed:1317577}; DE AltName: Full=Nax channel {ECO:0000303|PubMed:35301303}; DE AltName: Full=Sodium channel protein type VII subunit alpha; GN Name=SCN7A {ECO:0000312|HGNC:HGNC:10594}; GN Synonyms=SCN6A {ECO:0000312|HGNC:HGNC:10594}; 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], TISSUE SPECIFICITY, AND VARIANTS ASN-41 AND RP ILE-958. RC TISSUE=Fetal skeletal muscle, and Heart; RX PubMed=1317577; DOI=10.1073/pnas.89.11.4893; RA George A.L. Jr., Knittle T.J., Tamkun M.M.; RT "Molecular cloning of an atypical voltage-gated sodium channel expressed in RT human heart and uterus: evidence for a distinct gene family."; RL Proc. Natl. Acad. Sci. U.S.A. 89:4893-4897(1992). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., RA Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 and RT 4."; RL Nature 434:724-731(2005). RN [3] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-843, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [4] RP FUNCTION, AND TRANSPORTER ACTIVITY. RX PubMed=26537257; DOI=10.1126/scitranslmed.aad0286; RA Xu W., Hong S.J., Zhong A., Xie P., Jia S., Xie Z., Zeitchek M., RA Niknam-Bienia S., Zhao J., Porterfield D.M., Surmeier D.J., Leung K.P., RA Galiano R.D., Mustoe T.A.; RT "Sodium channel Nax is a regulator in epithelial sodium homeostasis."; RL Sci. Transl. Med. 7:312ra177-312ra177(2015). RN [5] {ECO:0007744|PDB:7TJ8, ECO:0007744|PDB:7TJ9} RP STRUCTURE BY ELECTRON MICROSCOPY (2.90 ANGSTROMS) OF 99-1504 IN COMPLEX RP WITH SCN3B, SUBUNIT, MUTAGENESIS OF PHE-724; ILE-1189 AND ILE-1492, RP FUNCTION, SUBCELLULAR LOCATION, TOPOLOGY, REPEAT, DISULFIDE BONDS, AND RP GLYCOSYLATION AT ASN-309 AND ASN-1103. 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). CC -!- FUNCTION: Sodium leak channel functioning as an osmosensor regulating CC sodium ion levels in various tissues and organs. While most sodium CC channels are voltage-gated, SCN7A is not and lets sodium flow through CC membrane along its concentration gradient (PubMed:26537257, CC PubMed:35301303). In glial cells of the central nervous system, senses CC body-fluid sodium levels and controls salt intake behavior as well as CC voluntary water intake through activation of nearby neurons to maintain CC appropriate sodium levels in the body (By similarity). By mediating CC sodium influx into keratinocytes, also plays a role in skin barrier CC homeostasis (PubMed:26537257). {ECO:0000250|UniProtKB:B1AYL1, CC ECO:0000269|PubMed:26537257, ECO:0000269|PubMed:35301303}. CC -!- CATALYTIC ACTIVITY: CC Reaction=Na(+)(in) = Na(+)(out); Xref=Rhea:RHEA:34963, CC ChEBI:CHEBI:29101; Evidence={ECO:0000269|PubMed:26537257}; CC -!- SUBUNIT: The sodium channel formed by SCN7A is probably a CC heterooligomeric complex consisting of the ion conducting pore forming CC alpha subunit SCN7A and regulatory beta subunits such as SCN3B CC (PubMed:35301303). Interacts with ATP1A1; activates ATP1A1 and thereby CC indirectly signals to nearby neurons to regulate sodium homeostasis (By CC similarity). {ECO:0000250|UniProtKB:B1AYL1, CC ECO:0000269|PubMed:35301303}. CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305|PubMed:35301303}; CC Multi-pass membrane protein {ECO:0000255}. CC -!- TISSUE SPECIFICITY: Heart and uterus. {ECO:0000269|PubMed:1317577}. 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 -!- SIMILARITY: Belongs to the sodium channel (TC 1.A.1.10) family. SCN7A CC subfamily. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M91556; AAA59899.1; -; mRNA. DR EMBL; AC074101; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC092583; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR CCDS; CCDS46442.1; -. DR PIR; A45380; A45380. DR RefSeq; NP_002967.2; NM_002976.3. DR RefSeq; XP_006712743.1; XM_006712680.2. DR RefSeq; XP_006712744.1; XM_006712681.3. DR RefSeq; XP_006712745.1; XM_006712682.3. DR RefSeq; XP_011509917.1; XM_011511615.2. DR RefSeq; XP_016860156.1; XM_017004667.1. DR PDB; 7TJ8; EM; 3.20 A; A=1-1682. DR PDB; 7TJ9; EM; 2.90 A; A=1-1682. DR PDBsum; 7TJ8; -. DR PDBsum; 7TJ9; -. DR AlphaFoldDB; Q01118; -. DR EMDB; EMD-25919; -. DR EMDB; EMD-25920; -. DR SMR; Q01118; -. DR IntAct; Q01118; 1. DR STRING; 9606.ENSP00000496114; -. DR BindingDB; Q01118; -. DR ChEMBL; CHEMBL3585; -. DR DrugBank; DB09088; Amylocaine. DR DrugBank; DB13746; Bioallethrin. DR DrugBank; DB05541; Brivaracetam. DR DrugBank; DB00564; Carbamazepine. DR DrugBank; DB01161; Chloroprocaine. DR DrugBank; DB00907; Cocaine. DR DrugBank; DB13269; Dichlorobenzyl alcohol. DR DrugBank; DB13961; Fish oil. DR DrugBank; DB00555; Lamotrigine. DR DrugBank; DB00776; Oxcarbazepine. DR DrugBank; DB11186; Pentoxyverine. DR DrugBank; DB09345; Pramocaine. DR DrugBank; DB01069; Promethazine. DR DrugBank; DB09342; Propoxycaine. DR DrugBank; DB00243; Ranolazine. DR DrugBank; DB09085; Tetracaine. DR DrugBank; DB00273; Topiramate. DR DrugBank; DB00313; Valproic acid. DR DrugCentral; Q01118; -. DR GlyConnect; 1753; 1 N-Linked glycan (1 site). DR GlyCosmos; Q01118; 5 sites, 1 glycan. DR GlyGen; Q01118; 6 sites, 1 N-linked glycan (1 site), 1 O-linked glycan (1 site). DR iPTMnet; Q01118; -. DR PhosphoSitePlus; Q01118; -. DR SwissPalm; Q01118; -. DR BioMuta; SCN7A; -. DR DMDM; 296452902; -. DR jPOST; Q01118; -. DR MassIVE; Q01118; -. DR PaxDb; 9606-ENSP00000386796; -. DR PeptideAtlas; Q01118; -. DR ProteomicsDB; 57921; -. DR Antibodypedia; 1383; 153 antibodies from 24 providers. DR DNASU; 6332; -. DR Ensembl; ENST00000441411.2; ENSP00000403846.2; ENSG00000136546.17. DR Ensembl; ENST00000643258.1; ENSP00000496114.1; ENSG00000136546.17. DR GeneID; 6332; -. DR KEGG; hsa:6332; -. DR MANE-Select; ENST00000643258.1; ENSP00000496114.1; NM_002976.4; NP_002967.2. DR UCSC; uc002udu.3; human. DR AGR; HGNC:10594; -. DR CTD; 6332; -. DR DisGeNET; 6332; -. DR GeneCards; SCN7A; -. DR HGNC; HGNC:10594; SCN7A. DR HPA; ENSG00000136546; Tissue enhanced (intestine, ovary). DR MIM; 182392; gene. DR neXtProt; NX_Q01118; -. DR OpenTargets; ENSG00000136546; -. DR PharmGKB; PA35008; -. DR VEuPathDB; HostDB:ENSG00000136546; -. DR eggNOG; KOG2301; Eukaryota. DR GeneTree; ENSGT00940000162042; -. DR HOGENOM; CLU_000540_5_0_1; -. DR InParanoid; Q01118; -. DR OMA; ENSWFKC; -. DR OrthoDB; 1110761at2759; -. DR PhylomeDB; Q01118; -. DR TreeFam; TF323985; -. DR PathwayCommons; Q01118; -. DR Reactome; R-HSA-445095; Interaction between L1 and Ankyrins. DR Reactome; R-HSA-5576892; Phase 0 - rapid depolarisation. DR SignaLink; Q01118; -. DR BioGRID-ORCS; 6332; 10 hits in 1143 CRISPR screens. DR ChiTaRS; SCN7A; human. DR GeneWiki; SCN7A; -. DR GenomeRNAi; 6332; -. DR Pharos; Q01118; Tclin. DR PRO; PR:Q01118; -. DR Proteomes; UP000005640; Chromosome 2. DR RNAct; Q01118; Protein. DR Bgee; ENSG00000136546; Expressed in trigeminal ganglion and 160 other cell types or tissues. DR ExpressionAtlas; Q01118; baseline and differential. DR GO; GO:0097386; C:glial cell projection; IEA:Ensembl. DR GO; GO:0005891; C:voltage-gated calcium channel complex; IBA:GO_Central. DR GO; GO:0001518; C:voltage-gated sodium channel complex; IEA:InterPro. DR GO; GO:0008331; F:high voltage-gated calcium channel activity; IBA:GO_Central. DR GO; GO:0005248; F:voltage-gated sodium channel activity; TAS:ProtInc. DR GO; GO:0098703; P:calcium ion import across plasma membrane; IBA:GO_Central. DR GO; GO:0019725; P:cellular homeostasis; IEA:Ensembl. DR GO; GO:0006936; P:muscle contraction; TAS:ProtInc. DR GO; GO:0009617; P:response to bacterium; IEA:Ensembl. DR GO; GO:0055078; P:sodium ion homeostasis; IEA:Ensembl. DR GO; GO:0006814; P:sodium ion transport; TAS:ProtInc. DR CDD; cd13433; Na_channel_gate; 1. DR Gene3D; 1.10.287.70; -; 4. DR Gene3D; 1.10.238.10; EF-hand; 1. DR Gene3D; 1.20.5.1190; iswi atpase; 1. DR Gene3D; 1.20.120.350; Voltage-gated potassium channels. Chain C; 4. DR InterPro; IPR005821; Ion_trans_dom. DR InterPro; IPR001696; Na_channel_asu. DR InterPro; IPR044564; Na_chnl_inactivation_gate. DR InterPro; IPR010526; Na_trans_assoc_dom. DR InterPro; IPR043203; VGCC_Ca_Na. DR InterPro; IPR027359; Volt_channel_dom_sf. DR PANTHER; PTHR10037:SF14; SODIUM CHANNEL PROTEIN; 1. DR PANTHER; PTHR10037; VOLTAGE-GATED CATION CHANNEL CALCIUM AND SODIUM; 1. DR Pfam; PF00520; Ion_trans; 4. DR Pfam; PF06512; Na_trans_assoc; 1. DR PRINTS; PR00170; NACHANNEL. DR SUPFAM; SSF81324; Voltage-gated potassium channels; 4. DR Genevisible; Q01118; HS. PE 1: Evidence at protein level; KW 3D-structure; Cell membrane; Disulfide bond; Glycoprotein; Membrane; KW Phosphoprotein; Reference proteome; Repeat; Transmembrane; KW Transmembrane helix. FT CHAIN 1..1682 FT /note="Sodium channel protein type 7 subunit alpha" FT /id="PRO_0000048499" FT TOPO_DOM 1..117 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:35301303, FT ECO:0007744|PDB:7TJ8, ECO:0007744|PDB:7TJ9" FT TRANSMEM 118..137 FT /note="Helical; Name=S1 of repeat I" FT /evidence="ECO:0000269|PubMed:35301303, FT ECO:0007744|PDB:7TJ8, ECO:0007744|PDB:7TJ9" FT TOPO_DOM 138..141 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:35301303, FT ECO:0007744|PDB:7TJ8, ECO:0007744|PDB:7TJ9" FT TRANSMEM 142..167 FT /note="Helical; Name=S2 of repeat I" FT /evidence="ECO:0000269|PubMed:35301303, FT ECO:0007744|PDB:7TJ8, ECO:0007744|PDB:7TJ9" FT TOPO_DOM 168..178 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:35301303, FT ECO:0007744|PDB:7TJ8, ECO:0007744|PDB:7TJ9" FT TRANSMEM 179..196 FT /note="Helical; Name=S3 of repeat I" FT /evidence="ECO:0000269|PubMed:35301303, FT ECO:0007744|PDB:7TJ8, ECO:0007744|PDB:7TJ9" FT TOPO_DOM 197..200 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:35301303, FT ECO:0007744|PDB:7TJ8, ECO:0007744|PDB:7TJ9" FT TRANSMEM 201..219 FT /note="Helical; Name=S4 of repeat I" FT /evidence="ECO:0000269|PubMed:35301303, FT ECO:0007744|PDB:7TJ8, ECO:0007744|PDB:7TJ9" FT TOPO_DOM 220..237 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:35301303, FT ECO:0007744|PDB:7TJ8, ECO:0007744|PDB:7TJ9" FT TRANSMEM 238..259 FT /note="Helical; Name=S5 of repeat I" FT /evidence="ECO:0000269|PubMed:35301303, FT ECO:0007744|PDB:7TJ8, ECO:0007744|PDB:7TJ9" FT TOPO_DOM 260..338 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:35301303, FT ECO:0007744|PDB:7TJ8, ECO:0007744|PDB:7TJ9" FT INTRAMEM 339..366 FT /note="Pore-forming" FT /evidence="ECO:0000250|UniProtKB:D0E0C2" FT TOPO_DOM 367 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:35301303, FT ECO:0007744|PDB:7TJ8, ECO:0007744|PDB:7TJ9" FT TRANSMEM 368..407 FT /note="Helical; Name=S6 of repeat I" FT /evidence="ECO:0000269|PubMed:35301303, FT ECO:0007744|PDB:7TJ8, ECO:0007744|PDB:7TJ9" FT TOPO_DOM 408..505 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:35301303, FT ECO:0007744|PDB:7TJ8, ECO:0007744|PDB:7TJ9" FT TRANSMEM 506..521 FT /note="Helical; Name=S1 of repeat II" FT /evidence="ECO:0000269|PubMed:35301303, FT ECO:0007744|PDB:7TJ8, ECO:0007744|PDB:7TJ9" FT TOPO_DOM 522..530 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:35301303, FT ECO:0007744|PDB:7TJ8, ECO:0007744|PDB:7TJ9" FT TRANSMEM 531..559 FT /note="Helical; Name=S2 of repeat II" FT /evidence="ECO:0000269|PubMed:35301303, FT ECO:0007744|PDB:7TJ8, ECO:0007744|PDB:7TJ9" FT TOPO_DOM 560..568 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:35301303, FT ECO:0007744|PDB:7TJ8, ECO:0007744|PDB:7TJ9" FT TRANSMEM 569..586 FT /note="Helical; Name=S3 of repeat II" FT /evidence="ECO:0000269|PubMed:35301303, FT ECO:0007744|PDB:7TJ8, ECO:0007744|PDB:7TJ9" FT TOPO_DOM 587..592 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:35301303, FT ECO:0007744|PDB:7TJ8, ECO:0007744|PDB:7TJ9" FT TRANSMEM 593..609 FT /note="Helical; Name=S4 of repeat II" FT /evidence="ECO:0000269|PubMed:35301303, FT ECO:0007744|PDB:7TJ8, ECO:0007744|PDB:7TJ9" FT TOPO_DOM 610..626 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:35301303, FT ECO:0007744|PDB:7TJ8, ECO:0007744|PDB:7TJ9" FT TRANSMEM 627..655 FT /note="Helical; Name=S5 of repeat II" FT /evidence="ECO:0000269|PubMed:35301303, FT ECO:0007744|PDB:7TJ8, ECO:0007744|PDB:7TJ9" FT TOPO_DOM 656..673 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:35301303, FT ECO:0007744|PDB:7TJ8, ECO:0007744|PDB:7TJ9" FT INTRAMEM 674..700 FT /note="Pore-forming" FT /evidence="ECO:0000250|UniProtKB:D0E0C2" FT TOPO_DOM 701 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:35301303, FT ECO:0007744|PDB:7TJ8, ECO:0007744|PDB:7TJ9" FT TRANSMEM 702..732 FT /note="Helical; Name=S6 of repeat II" FT /evidence="ECO:0000269|PubMed:35301303, FT ECO:0007744|PDB:7TJ8, ECO:0007744|PDB:7TJ9" FT TOPO_DOM 733..934 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:35301303, FT ECO:0007744|PDB:7TJ8, ECO:0007744|PDB:7TJ9" FT TRANSMEM 935..953 FT /note="Helical; Name=S1 of repeat III" FT /evidence="ECO:0000269|PubMed:35301303, FT ECO:0007744|PDB:7TJ8, ECO:0007744|PDB:7TJ9" FT TOPO_DOM 954..961 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:35301303, FT ECO:0007744|PDB:7TJ8, ECO:0007744|PDB:7TJ9" FT TRANSMEM 962..990 FT /note="Helical; Name=S2 of repeat III" FT /evidence="ECO:0000269|PubMed:35301303, FT ECO:0007744|PDB:7TJ8, ECO:0007744|PDB:7TJ9" FT TOPO_DOM 991..998 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:35301303, FT ECO:0007744|PDB:7TJ8, ECO:0007744|PDB:7TJ9" FT TRANSMEM 999..1020 FT /note="Helical; Name=S3 of repeat III" FT /evidence="ECO:0000269|PubMed:35301303, FT ECO:0007744|PDB:7TJ8, ECO:0007744|PDB:7TJ9" FT TOPO_DOM 1021 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:35301303, FT ECO:0007744|PDB:7TJ8, ECO:0007744|PDB:7TJ9" FT TRANSMEM 1022..1040 FT /note="Helical; Name=S4 of repeat III" FT /evidence="ECO:0000269|PubMed:35301303, FT ECO:0007744|PDB:7TJ8, ECO:0007744|PDB:7TJ9" FT TOPO_DOM 1041..1055 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:35301303, FT ECO:0007744|PDB:7TJ8, ECO:0007744|PDB:7TJ9" FT TRANSMEM 1056..1080 FT /note="Helical; Name=S5 of repeat III" FT /evidence="ECO:0000269|PubMed:35301303, FT ECO:0007744|PDB:7TJ8, ECO:0007744|PDB:7TJ9" FT TOPO_DOM 1081..1127 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:35301303, FT ECO:0007744|PDB:7TJ8, ECO:0007744|PDB:7TJ9" FT INTRAMEM 1128..1154 FT /note="Pore-forming" FT /evidence="ECO:0000250|UniProtKB:D0E0C2" FT TOPO_DOM 1155..1167 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:35301303, FT ECO:0007744|PDB:7TJ8, ECO:0007744|PDB:7TJ9" FT TRANSMEM 1168..1202 FT /note="Helical; Name=S6 of repeat III" FT /evidence="ECO:0000269|PubMed:35301303, FT ECO:0007744|PDB:7TJ8, ECO:0007744|PDB:7TJ9" FT TOPO_DOM 1203..1250 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:35301303, FT ECO:0007744|PDB:7TJ8, ECO:0007744|PDB:7TJ9" FT TRANSMEM 1251..1272 FT /note="Helical; Name=S1 of repeat IV" FT /evidence="ECO:0000269|PubMed:35301303, FT ECO:0007744|PDB:7TJ8, ECO:0007744|PDB:7TJ9" FT TOPO_DOM 1273..1276 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:35301303, FT ECO:0007744|PDB:7TJ8, ECO:0007744|PDB:7TJ9" FT TRANSMEM 1277..1305 FT /note="Helical; Name=S2 of repeat IV" FT /evidence="ECO:0000269|PubMed:35301303, FT ECO:0007744|PDB:7TJ8, ECO:0007744|PDB:7TJ9" FT TOPO_DOM 1306..1312 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:35301303, FT ECO:0007744|PDB:7TJ8, ECO:0007744|PDB:7TJ9" FT TRANSMEM 1313..1338 FT /note="Helical; Name=S3 of repeat IV" FT /evidence="ECO:0000269|PubMed:35301303, FT ECO:0007744|PDB:7TJ8, ECO:0007744|PDB:7TJ9" FT TOPO_DOM 1339..1341 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:35301303, FT ECO:0007744|PDB:7TJ8, ECO:0007744|PDB:7TJ9" FT TRANSMEM 1342..1362 FT /note="Helical; Name=S4 of repeat IV" FT /evidence="ECO:0000269|PubMed:35301303, FT ECO:0007744|PDB:7TJ8, ECO:0007744|PDB:7TJ9" FT TOPO_DOM 1363..1377 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:35301303, FT ECO:0007744|PDB:7TJ8, ECO:0007744|PDB:7TJ9" FT TRANSMEM 1378..1402 FT /note="Helical; Name=S5 of repeat IV" FT /evidence="ECO:0000269|PubMed:35301303, FT ECO:0007744|PDB:7TJ8, ECO:0007744|PDB:7TJ9" FT TOPO_DOM 1403..1420 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:35301303, FT ECO:0007744|PDB:7TJ8, ECO:0007744|PDB:7TJ9" FT INTRAMEM 1421..1444 FT /note="Pore-forming" FT /evidence="ECO:0000250|UniProtKB:D0E0C2" FT TOPO_DOM 1445..1468 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:35301303, FT ECO:0007744|PDB:7TJ8, ECO:0007744|PDB:7TJ9" FT TRANSMEM 1469..1504 FT /note="Helical; Name=S6 of repeat IV" FT /evidence="ECO:0000269|PubMed:35301303, FT ECO:0007744|PDB:7TJ8, ECO:0007744|PDB:7TJ9" FT TOPO_DOM 1505..1682 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:35301303, FT ECO:0007744|PDB:7TJ8, ECO:0007744|PDB:7TJ9" FT REPEAT 100..401 FT /note="I" FT /evidence="ECO:0000305|PubMed:35301303" FT REPEAT 487..758 FT /note="II" FT /evidence="ECO:0000305|PubMed:35301303" FT REPEAT 916..1224 FT /note="III" FT /evidence="ECO:0000305|PubMed:35301303" FT REPEAT 1233..1531 FT /note="IV" FT /evidence="ECO:0000305|PubMed:35301303" FT REGION 801..871 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 802..816 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 817..840 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 845..863 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 442 FT /note="Phosphoserine; by PKA" FT /evidence="ECO:0000255" FT MOD_RES 777 FT /note="Phosphothreonine; by PKA" FT /evidence="ECO:0000255" FT MOD_RES 843 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 869 FT /note="Phosphoserine; by PKA" FT /evidence="ECO:0000255" FT MOD_RES 905 FT /note="Phosphoserine; by PKA" FT /evidence="ECO:0000255" FT CARBOHYD 276 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 281 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 309 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:35301303, FT ECO:0007744|PDB:7TJ8" FT CARBOHYD 1103 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:35301303, FT ECO:0007744|PDB:7TJ8, ECO:0007744|PDB:7TJ9" FT CARBOHYD 1113 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 267..307 FT /evidence="ECO:0000269|PubMed:35301303, FT ECO:0007744|PDB:7TJ9" FT DISULFID 658..664 FT /evidence="ECO:0000269|PubMed:35301303, FT ECO:0007744|PDB:7TJ9" FT DISULFID 696..705 FT /evidence="ECO:0000269|PubMed:35301303, FT ECO:0007744|PDB:7TJ8, ECO:0007744|PDB:7TJ9" FT DISULFID 1087..1107 FT /evidence="ECO:0000269|PubMed:35301303, FT ECO:0007744|PDB:7TJ8, ECO:0007744|PDB:7TJ9" FT DISULFID 1451..1466 FT /evidence="ECO:0000269|PubMed:35301303, FT ECO:0007744|PDB:7TJ9" FT VARIANT 41 FT /note="T -> N (in dbSNP:rs7565062)" FT /evidence="ECO:0000269|PubMed:1317577" FT /id="VAR_063120" FT VARIANT 407 FT /note="I -> V (in dbSNP:rs11888208)" FT /id="VAR_024410" FT VARIANT 600 FT /note="M -> L (in dbSNP:rs34183637)" FT /id="VAR_055641" FT VARIANT 958 FT /note="M -> I (in dbSNP:rs6738031)" FT /evidence="ECO:0000269|PubMed:1317577" FT /id="VAR_063121" FT VARIANT 1313 FT /note="A -> V (in dbSNP:rs6760593)" FT /id="VAR_055642" FT VARIANT 1516 FT /note="R -> K (in dbSNP:rs34799257)" FT /id="VAR_055643" FT VARIANT 1596 FT /note="V -> L (in dbSNP:rs3791251)" FT /id="VAR_055644" FT VARIANT 1657 FT /note="D -> G (in dbSNP:rs35344714)" FT /id="VAR_055645" FT MUTAGEN 724 FT /note="F->E: Increased non-selective monoatomic cation leak FT channel activity; when associated with T-1189 and T-1492." FT /evidence="ECO:0000269|PubMed:35301303" FT MUTAGEN 724 FT /note="F->Q: Increased non-selective monoatomic cation leak FT channel activity; when associated with T-1189 and T-1492." FT /evidence="ECO:0000269|PubMed:35301303" FT MUTAGEN 1189 FT /note="I->E: Increased non-selective monoatomic cation leak FT channel activity; when associated with Q-724 and T-1492." FT /evidence="ECO:0000269|PubMed:35301303" FT MUTAGEN 1189 FT /note="I->T: Increased non-selective monoatomic cation leak FT channel activity; when associated with Q-724 and T-1492." FT /evidence="ECO:0000269|PubMed:35301303" FT MUTAGEN 1492 FT /note="I->E: Increased non-selective monoatomic cation leak FT channel activity; when associated with Q-724 and T-1189." FT /evidence="ECO:0000269|PubMed:35301303" FT MUTAGEN 1492 FT /note="I->T: Increased non-selective monoatomic cation leak FT channel activity; when associated with Q-724 and T-1189." FT /evidence="ECO:0000269|PubMed:35301303" FT CONFLICT 361 FT /note="Q -> L (in Ref. 1; AAA59899)" FT /evidence="ECO:0000305" FT HELIX 106..115 FT /evidence="ECO:0007829|PDB:7TJ9" FT HELIX 118..135 FT /evidence="ECO:0007829|PDB:7TJ9" FT HELIX 144..166 FT /evidence="ECO:0007829|PDB:7TJ9" FT STRAND 170..174 FT /evidence="ECO:0007829|PDB:7TJ9" FT TURN 175..177 FT /evidence="ECO:0007829|PDB:7TJ9" FT HELIX 179..195 FT /evidence="ECO:0007829|PDB:7TJ9" FT HELIX 202..210 FT /evidence="ECO:0007829|PDB:7TJ9" FT HELIX 211..216 FT /evidence="ECO:0007829|PDB:7TJ9" FT TURN 217..219 FT /evidence="ECO:0007829|PDB:7TJ9" FT HELIX 221..236 FT /evidence="ECO:0007829|PDB:7TJ9" FT HELIX 238..259 FT /evidence="ECO:0007829|PDB:7TJ9" FT HELIX 262..264 FT /evidence="ECO:0007829|PDB:7TJ9" FT STRAND 265..270 FT /evidence="ECO:0007829|PDB:7TJ9" FT HELIX 286..288 FT /evidence="ECO:0007829|PDB:7TJ8" FT TURN 292..294 FT /evidence="ECO:0007829|PDB:7TJ9" FT STRAND 320..324 FT /evidence="ECO:0007829|PDB:7TJ9" FT HELIX 330..332 FT /evidence="ECO:0007829|PDB:7TJ9" FT HELIX 341..350 FT /evidence="ECO:0007829|PDB:7TJ9" FT HELIX 355..365 FT /evidence="ECO:0007829|PDB:7TJ9" FT HELIX 368..370 FT /evidence="ECO:0007829|PDB:7TJ9" FT HELIX 371..381 FT /evidence="ECO:0007829|PDB:7TJ9" FT HELIX 384..403 FT /evidence="ECO:0007829|PDB:7TJ9" FT HELIX 508..523 FT /evidence="ECO:0007829|PDB:7TJ9" FT HELIX 532..558 FT /evidence="ECO:0007829|PDB:7TJ9" FT HELIX 561..564 FT /evidence="ECO:0007829|PDB:7TJ9" FT HELIX 568..584 FT /evidence="ECO:0007829|PDB:7TJ9" FT STRAND 585..590 FT /evidence="ECO:0007829|PDB:7TJ8" FT HELIX 596..609 FT /evidence="ECO:0007829|PDB:7TJ9" FT HELIX 611..655 FT /evidence="ECO:0007829|PDB:7TJ9" FT HELIX 657..659 FT /evidence="ECO:0007829|PDB:7TJ9" FT HELIX 674..685 FT /evidence="ECO:0007829|PDB:7TJ9" FT HELIX 691..699 FT /evidence="ECO:0007829|PDB:7TJ9" FT HELIX 702..732 FT /evidence="ECO:0007829|PDB:7TJ9" FT HELIX 922..932 FT /evidence="ECO:0007829|PDB:7TJ9" FT HELIX 934..949 FT /evidence="ECO:0007829|PDB:7TJ9" FT HELIX 950..953 FT /evidence="ECO:0007829|PDB:7TJ9" FT TURN 956..960 FT /evidence="ECO:0007829|PDB:7TJ9" FT HELIX 962..990 FT /evidence="ECO:0007829|PDB:7TJ9" FT HELIX 992..996 FT /evidence="ECO:0007829|PDB:7TJ9" FT HELIX 999..1016 FT /evidence="ECO:0007829|PDB:7TJ9" FT TURN 1021..1023 FT /evidence="ECO:0007829|PDB:7TJ9" FT HELIX 1024..1035 FT /evidence="ECO:0007829|PDB:7TJ9" FT HELIX 1036..1040 FT /evidence="ECO:0007829|PDB:7TJ9" FT HELIX 1042..1055 FT /evidence="ECO:0007829|PDB:7TJ9" FT HELIX 1056..1058 FT /evidence="ECO:0007829|PDB:7TJ8" FT HELIX 1059..1080 FT /evidence="ECO:0007829|PDB:7TJ9" FT STRAND 1086..1088 FT /evidence="ECO:0007829|PDB:7TJ9" FT TURN 1090..1092 FT /evidence="ECO:0007829|PDB:7TJ9" FT TURN 1098..1100 FT /evidence="ECO:0007829|PDB:7TJ9" FT HELIX 1104..1108 FT /evidence="ECO:0007829|PDB:7TJ9" FT STRAND 1111..1113 FT /evidence="ECO:0007829|PDB:7TJ8" FT STRAND 1117..1119 FT /evidence="ECO:0007829|PDB:7TJ9" FT HELIX 1128..1139 FT /evidence="ECO:0007829|PDB:7TJ9" FT HELIX 1144..1151 FT /evidence="ECO:0007829|PDB:7TJ9" FT STRAND 1156..1159 FT /evidence="ECO:0007829|PDB:7TJ9" FT HELIX 1167..1169 FT /evidence="ECO:0007829|PDB:7TJ9" FT HELIX 1170..1179 FT /evidence="ECO:0007829|PDB:7TJ9" FT HELIX 1182..1203 FT /evidence="ECO:0007829|PDB:7TJ9" FT STRAND 1208..1210 FT /evidence="ECO:0007829|PDB:7TJ9" FT HELIX 1212..1224 FT /evidence="ECO:0007829|PDB:7TJ9" FT HELIX 1246..1249 FT /evidence="ECO:0007829|PDB:7TJ9" FT HELIX 1251..1268 FT /evidence="ECO:0007829|PDB:7TJ9" FT STRAND 1272..1274 FT /evidence="ECO:0007829|PDB:7TJ9" FT HELIX 1277..1304 FT /evidence="ECO:0007829|PDB:7TJ9" FT TURN 1306..1311 FT /evidence="ECO:0007829|PDB:7TJ9" FT HELIX 1313..1334 FT /evidence="ECO:0007829|PDB:7TJ9" FT HELIX 1344..1350 FT /evidence="ECO:0007829|PDB:7TJ9" FT HELIX 1351..1357 FT /evidence="ECO:0007829|PDB:7TJ9" FT STRAND 1358..1362 FT /evidence="ECO:0007829|PDB:7TJ9" FT HELIX 1364..1402 FT /evidence="ECO:0007829|PDB:7TJ9" FT STRAND 1413..1419 FT /evidence="ECO:0007829|PDB:7TJ9" FT HELIX 1420..1431 FT /evidence="ECO:0007829|PDB:7TJ9" FT HELIX 1436..1443 FT /evidence="ECO:0007829|PDB:7TJ9" FT HELIX 1444..1446 FT /evidence="ECO:0007829|PDB:7TJ9" FT TURN 1447..1449 FT /evidence="ECO:0007829|PDB:7TJ9" FT HELIX 1469..1502 FT /evidence="ECO:0007829|PDB:7TJ9" SQ SEQUENCE 1682 AA; 193493 MW; 38CD8D41975BCE18 CRC64; MLASPEPKGL VPFTKESFEL IKQHIAKTHN EDHEEEDLKP TPDLEVGKKL PFIYGNLSQG MVSEPLEDVD PYYYKKKNTF IVLNKNRTIF RFNAASILCT LSPFNCIRRT TIKVLVHPFF QLFILISVLI DCVFMSLTNL PKWRPVLENT LLGIYTFEIL VKLFARGVWA GSFSFLGDPW NWLDFSVTVF EVIIRYSPLD FIPTLQTART LRILKIIPLN QGLKSLVGVL IHCLKQLIGV IILTLFFLSI FSLIGMGLFM GNLKHKCFRW PQENENETLH NRTGNPYYIR ETENFYYLEG ERYALLCGNR TDAGQCPEGY VCVKAGINPD QGFTNFDSFG WALFALFRLM AQDYPEVLYH QILYASGKVY MIFFVVVSFL FSFYMASLFL GILAMAYEEE KQRVGEISKK IEPKFQQTGK ELQEGNETDE AKTIQIEMKK RSPISTDTSL DVLEDATLRH KEELEKSKKI CPLYWYKFAK TFLIWNCSPC WLKLKEFVHR IIMAPFTDLF LIICIILNVC FLTLEHYPMS KQTNTLLNIG NLVFIGIFTA EMIFKIIAMH PYGYFQVGWN IFDSMIVFHG LIELCLANVA GMALLRLFRM LRIFKLGKYW PTFQILMWSL SNSWVALKDL VLLLFTFIFF SAAFGMKLFG KNYEEFVCHI DKDCQLPRWH MHDFFHSFLN VFRILCGEWV ETLWDCMEVA GQSWCIPFYL MVILIGNLLV LYLFLALVSS FSSCKDVTAE ENNEAKNLQL AVARIKKGIN YVLLKILCKT QNVPKDTMDH VNEVYVKEDI SDHTLSELSN TQDFLKDKEK SSGTEKNATE NESQSLIPSP SVSETVPIAS GESDIENLDN KEIQSKSGDG GSKEKIKQSS SSECSTVDIA ISEEEEMFYG GERSKHLKNG CRRGSSLGQI SGASKKGKIW QNIRKTCCKI VENNWFKCFI GLVTLLSTGT LAFEDIYMDQ RKTIKILLEY ADMIFTYIFI LEMLLKWMAY GFKAYFSNGW YRLDFVVVIV FCLSLIGKTR EELKPLISMK FLRPLRVLSQ FERMKVVVRA LIKTTLPTLN VFLVCLMIWL IFSIMGVDLF AGRFYECIDP TSGERFPSSE VMNKSRCESL LFNESMLWEN AKMNFDNVGN GFLSLLQVAT FNGWITIMNS AIDSVAVNIQ PHFEVNIYMY CYFINFIIFG VFLPLSMLIT VIIDNFNKHK IKLGGSNIFI TVKQRKQYRR LKKLMYEDSQ RPVPRPLNKL QGFIFDVVTS QAFNVIVMVL ICFQAIAMMI DTDVQSLQMS IALYWINSIF VMLYTMECIL KLIAFRCFYF TIAWNIFDFM VVIFSITGLC LPMTVGSYLV PPSLVQLILL SRIIHMLRLG KGPKVFHNLM LPLMLSLPAL LNIILLIFLV MFIYAVFGMY NFAYVKKEAG INDVSNFETF GNSMLCLFQV AIFAGWDGML DAIFNSKWSD CDPDKINPGT QVRGDCGNPS VGIFYFVSYI LISWLIIVNM YIVVVMEFLN IASKKKNKTL SEDDFRKFFQ VWKRFDPDRT QYIDSSKLSD FAAALDPPLF MAKPNKGQLI ALDLPMAVGD RIHCLDILLA FTKRVMGQDV RMEKVVSEIE SGFLLANPFK ITCEPITTTL KRKQEAVSAT IIQRAYKNYR LRRNDKNTSD IHMIDGDRDV HATKEGAYFD KAKEKSPIQS QI //