KCNT1_HUMAN
ID KCNT1_HUMAN Reviewed; 1230 AA.
AC Q5JUK3; B3KXF7; B7ZVY4; B9EGP2; G5E9V0; Q9P2C5;
DT 30-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT 30-AUG-2005, sequence version 2.
DT 03-AUG-2022, entry version 158.
DE RecName: Full=Potassium channel subfamily T member 1;
DE AltName: Full=KCa4.1;
GN Name=KCNT1; Synonyms=KIAA1422;
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 [LARGE SCALE MRNA] (ISOFORM 4).
RC TISSUE=Hippocampus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-1103 (ISOFORM 2), AND TISSUE
RP SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=10718198; DOI=10.1093/dnares/7.1.65;
RA Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XVI. The
RT complete sequences of 150 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 7:65-73(2000).
RN [6]
RP INTERACTION WITH FMR1.
RX PubMed=20512134; DOI=10.1038/nn.2563;
RA Brown M.R., Kronengold J., Gazula V.R., Chen Y., Strumbos J.G.,
RA Sigworth F.J., Navaratnam D., Kaczmarek L.K.;
RT "Fragile X mental retardation protein controls gating of the sodium-
RT activated potassium channel Slack.";
RL Nat. Neurosci. 13:819-821(2010).
RN [7]
RP VARIANTS ENFL5 GLN-379; HIS-777; ILE-877 AND CYS-909.
RX PubMed=23086396; DOI=10.1038/ng.2440;
RA Heron S.E., Smith K.R., Bahlo M., Nobili L., Kahana E., Licchetta L.,
RA Oliver K.L., Mazarib A., Afawi Z., Korczyn A., Plazzi G., Petrou S.,
RA Berkovic S.F., Scheffer I.E., Dibbens L.M.;
RT "Missense mutations in the sodium-gated potassium channel gene KCNT1 cause
RT severe autosomal dominant nocturnal frontal lobe epilepsy.";
RL Nat. Genet. 44:1188-1190(2012).
RN [8]
RP VARIANTS DEE14 GLN-409; HIS-455; MET-741 AND THR-915, AND CHARACTERIZATION
RP OF VARIANTS DEE14 GLN-409 AND THR-915.
RX PubMed=23086397; DOI=10.1038/ng.2441;
RA Barcia G., Fleming M.R., Deligniere A., Gazula V.R., Brown M.R.,
RA Langouet M., Chen H., Kronengold J., Abhyankar A., Cilio R., Nitschke P.,
RA Kaminska A., Boddaert N., Casanova J.L., Desguerre I., Munnich A.,
RA Dulac O., Kaczmarek L.K., Colleaux L., Nabbout R.;
RT "De novo gain-of-function KCNT1 channel mutations cause malignant migrating
RT partial seizures of infancy.";
RL Nat. Genet. 44:1255-1259(2012).
RN [9]
RP VARIANT DEE14 SER-269.
RX PubMed=24029078; DOI=10.1016/j.gene.2013.08.096;
RA Ishii A., Shioda M., Okumura A., Kidokoro H., Sakauchi M., Shimada S.,
RA Shimizu T., Osawa M., Hirose S., Yamamoto T.;
RT "A recurrent KCNT1 mutation in two sporadic cases with malignant migrating
RT partial seizures in infancy.";
RL Gene 531:467-471(2013).
RN [10]
RP VARIANTS DEE14 ILE-562 AND GLN-1088.
RX PubMed=23708187; DOI=10.1038/ng.2646;
RA Carvill G.L., Heavin S.B., Yendle S.C., McMahon J.M., O'Roak B.J., Cook J.,
RA Khan A., Dorschner M.O., Weaver M., Calvert S., Malone S., Wallace G.,
RA Stanley T., Bye A.M., Bleasel A., Howell K.B., Kivity S., Mackay M.T.,
RA Rodriguez-Casero V., Webster R., Korczyn A., Afawi Z., Zelnick N.,
RA Lerman-Sagie T., Lev D., Moeller R.S., Gill D., Andrade D.M., Freeman J.L.,
RA Sadleir L.G., Shendure J., Berkovic S.F., Scheffer I.E., Mefford H.C.;
RT "Targeted resequencing in epileptic encephalopathies identifies de novo
RT mutations in CHD2 and SYNGAP1.";
RL Nat. Genet. 45:825-830(2013).
RN [11]
RP VARIANT DEE14 THR-947, AND CHARACTERIZATION OF VARIANT DEE14 THR-947.
RX PubMed=24463883; DOI=10.1093/hmg/ddu030;
RG WGS500 Consortium;
RA Martin H.C., Kim G.E., Pagnamenta A.T., Murakami Y., Carvill G.L.,
RA Meyer E., Copley R.R., Rimmer A., Barcia G., Fleming M.R., Kronengold J.,
RA Brown M.R., Hudspith K.A., Broxholme J., Kanapin A., Cazier J.B.,
RA Kinoshita T., Nabbout R., Bentley D., McVean G., Heavin S., Zaiwalla Z.,
RA McShane T., Mefford H.C., Shears D., Stewart H., Kurian M.A.,
RA Scheffer I.E., Blair E., Donnelly P., Kaczmarek L.K., Taylor J.C.;
RT "Clinical whole-genome sequencing in severe early-onset epilepsy reveals
RT new genes and improves molecular diagnosis.";
RL Hum. Mol. Genet. 23:3200-3211(2014).
RN [12]
RP VARIANTS DEE14 SER-269; LYS-877 AND THR-915.
RX PubMed=26993267; DOI=10.1136/jmedgenet-2015-103263;
RA Trump N., McTague A., Brittain H., Papandreou A., Meyer E., Ngoh A.,
RA Palmer R., Morrogh D., Boustred C., Hurst J.A., Jenkins L., Kurian M.A.,
RA Scott R.H.;
RT "Improving diagnosis and broadening the phenotypes in early-onset seizure
RT and severe developmental delay disorders through gene panel analysis.";
RL J. Med. Genet. 53:310-317(2016).
RN [13]
RP VARIANTS DEE14 VAL-497 AND GLU-928.
RX PubMed=27864847; DOI=10.1002/humu.23149;
RG Clinical Study Group;
RA Parrini E., Marini C., Mei D., Galuppi A., Cellini E., Pucatti D.,
RA Chiti L., Rutigliano D., Bianchini C., Virdo S., De Vita D., Bigoni S.,
RA Barba C., Mari F., Montomoli M., Pisano T., Rosati A., Guerrini R.;
RT "Diagnostic targeted resequencing in 349 patients with drug-resistant
RT pediatric epilepsies identifies causative mutations in 30 different
RT genes.";
RL Hum. Mutat. 38:216-225(2017).
CC -!- FUNCTION: Outwardly rectifying potassium channel subunit that may
CC coassemble with other Slo-type channel subunits. Activated by high
CC intracellular sodium or chloride levels. Activated upon stimulation of
CC G-protein coupled receptors, such as CHRM1 and GRIA1. May be regulated
CC by calcium in the absence of sodium ions (in vitro) (By similarity).
CC {ECO:0000250}.
CC -!- SUBUNIT: Interacts (via C-terminus) with FMR1; this interaction alters
CC gating properties of KCNT1 (PubMed:20512134). Interacts with CRBN via
CC its cytoplasmic C-terminus (By similarity).
CC {ECO:0000250|UniProtKB:Q9Z258, ECO:0000269|PubMed:20512134}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Multi-pass membrane
CC protein {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q5JUK3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q5JUK3-2; Sequence=VSP_015470, VSP_015471;
CC Name=3;
CC IsoId=Q5JUK3-3; Sequence=VSP_015470, VSP_015471, VSP_044476;
CC Name=4;
CC IsoId=Q5JUK3-4; Sequence=VSP_055700, VSP_055701, VSP_015471;
CC -!- TISSUE SPECIFICITY: Highest expression in liver, brain and spinal cord.
CC Lowest expression in skeletal muscle. {ECO:0000269|PubMed:10718198}.
CC -!- PTM: Phosphorylated by protein kinase C. Phosphorylation of the C-
CC terminal domain increases channel activity (By similarity).
CC {ECO:0000250}.
CC -!- DISEASE: Developmental and epileptic encephalopathy 14 (DEE14)
CC [MIM:614959]: A rare epileptic encephalopathy of infancy that combines
CC pharmacoresistant seizures with developmental delay. This severe
CC neurologic disorder is characterized by onset in the first 6 months of
CC life of refractory focal seizures and arrest of psychomotor
CC development. Ictal EEG shows discharges that arise randomly from
CC various areas of both hemispheres and migrate from one brain region to
CC another. {ECO:0000269|PubMed:23086397, ECO:0000269|PubMed:23708187,
CC ECO:0000269|PubMed:24029078, ECO:0000269|PubMed:24463883,
CC ECO:0000269|PubMed:26993267, ECO:0000269|PubMed:27864847}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Epilepsy, nocturnal frontal lobe, 5 (ENFL5) [MIM:615005]: An
CC autosomal dominant focal epilepsy syndrome characterized by childhood
CC onset of clusters of motor seizures during sleep. Some patients may
CC develop behavioral or psychiatric manifestations and/or intellectual
CC disability. The phenotype is more severe than observed in other genetic
CC forms of nocturnal frontal lobe epilepsy.
CC {ECO:0000269|PubMed:23086396}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the potassium channel family. Calcium-activated
CC (TC 1.A.1.3) subfamily. KCa4.1/KCNT1 sub-subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA92660.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AK127272; BAG54469.1; -; mRNA.
DR EMBL; AL158822; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471090; EAW88180.1; -; Genomic_DNA.
DR EMBL; BC136618; AAI36619.1; -; mRNA.
DR EMBL; BC171770; AAI71770.1; -; mRNA.
DR EMBL; AB037843; BAA92660.1; ALT_INIT; mRNA.
DR CCDS; CCDS35175.2; -. [Q5JUK3-3]
DR CCDS; CCDS65188.1; -. [Q5JUK3-4]
DR RefSeq; NP_001258932.1; NM_001272003.1. [Q5JUK3-4]
DR RefSeq; NP_065873.2; NM_020822.2. [Q5JUK3-3]
DR AlphaFoldDB; Q5JUK3; -.
DR SMR; Q5JUK3; -.
DR IntAct; Q5JUK3; 2.
DR STRING; 9606.ENSP00000360822; -.
DR BindingDB; Q5JUK3; -.
DR ChEMBL; CHEMBL4739688; -.
DR DrugCentral; Q5JUK3; -.
DR GuidetoPHARMACOLOGY; 385; -.
DR GlyGen; Q5JUK3; 2 sites.
DR iPTMnet; Q5JUK3; -.
DR PhosphoSitePlus; Q5JUK3; -.
DR BioMuta; KCNT1; -.
DR DMDM; 73920089; -.
DR MassIVE; Q5JUK3; -.
DR PaxDb; Q5JUK3; -.
DR PeptideAtlas; Q5JUK3; -.
DR PRIDE; Q5JUK3; -.
DR ProteomicsDB; 34049; -.
DR ProteomicsDB; 63278; -. [Q5JUK3-1]
DR ProteomicsDB; 63279; -. [Q5JUK3-2]
DR ProteomicsDB; 7527; -.
DR ABCD; Q5JUK3; 1 sequenced antibody.
DR Antibodypedia; 32072; 178 antibodies from 26 providers.
DR DNASU; 57582; -.
DR Ensembl; ENST00000371757.7; ENSP00000360822.2; ENSG00000107147.14. [Q5JUK3-3]
DR Ensembl; ENST00000487664.5; ENSP00000417851.2; ENSG00000107147.14. [Q5JUK3-2]
DR Ensembl; ENST00000488444.6; ENSP00000419007.3; ENSG00000107147.14. [Q5JUK3-1]
DR Ensembl; ENST00000628528.2; ENSP00000486374.1; ENSG00000107147.14. [Q5JUK3-4]
DR GeneID; 57582; -.
DR KEGG; hsa:57582; -.
DR MANE-Select; ENST00000371757.7; ENSP00000360822.2; NM_020822.3; NP_065873.2. [Q5JUK3-3]
DR UCSC; uc011mdq.3; human. [Q5JUK3-1]
DR CTD; 57582; -.
DR DisGeNET; 57582; -.
DR GeneCards; KCNT1; -.
DR GeneReviews; KCNT1; -.
DR HGNC; HGNC:18865; KCNT1.
DR HPA; ENSG00000107147; Tissue enhanced (brain, lymphoid tissue, skeletal muscle).
DR MalaCards; KCNT1; -.
DR MIM; 608167; gene.
DR MIM; 614959; phenotype.
DR MIM; 615005; phenotype.
DR neXtProt; NX_Q5JUK3; -.
DR OpenTargets; ENSG00000107147; -.
DR Orphanet; 98784; Autosomal dominant nocturnal frontal lobe epilepsy.
DR Orphanet; 293181; Malignant migrating focal seizures of infancy.
DR PharmGKB; PA38725; -.
DR VEuPathDB; HostDB:ENSG00000107147; -.
DR eggNOG; KOG3193; Eukaryota.
DR GeneTree; ENSGT00940000156880; -.
DR InParanoid; Q5JUK3; -.
DR OrthoDB; 858812at2759; -.
DR PhylomeDB; Q5JUK3; -.
DR TreeFam; TF314283; -.
DR PathwayCommons; Q5JUK3; -.
DR SignaLink; Q5JUK3; -.
DR BioGRID-ORCS; 57582; 6 hits in 1062 CRISPR screens.
DR ChiTaRS; KCNT1; human.
DR GeneWiki; KCNT1; -.
DR GenomeRNAi; 57582; -.
DR Pharos; Q5JUK3; Tchem.
DR PRO; PR:Q5JUK3; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; Q5JUK3; protein.
DR Bgee; ENSG00000107147; Expressed in right hemisphere of cerebellum and 94 other tissues.
DR ExpressionAtlas; Q5JUK3; baseline and differential.
DR Genevisible; Q5JUK3; HS.
DR GO; GO:0016021; C:integral component of membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0005228; F:intracellular sodium activated potassium channel activity; IBA:GO_Central.
DR GO; GO:0015271; F:outward rectifier potassium channel activity; IBA:GO_Central.
DR InterPro; IPR003929; K_chnl_BK_asu.
DR InterPro; IPR013099; K_chnl_dom.
DR Pfam; PF03493; BK_channel_a; 1.
DR Pfam; PF07885; Ion_trans_2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Calcium; Cell membrane; Disease variant; Epilepsy;
KW Glycoprotein; Ion channel; Ion transport; Membrane; Phosphoprotein;
KW Potassium; Potassium channel; Potassium transport; Reference proteome;
KW Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..1230
FT /note="Potassium channel subfamily T member 1"
FT /id="PRO_0000054090"
FT TOPO_DOM 1..97
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 98..118
FT /note="Helical; Name=Segment S1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 119..155
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 156..176
FT /note="Helical; Name=Segment S2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 177..187
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 188..208
FT /note="Helical; Name=Segment S3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 209..213
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 214..226
FT /note="Helical; Name=Segment S4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 227..251
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 252..272
FT /note="Helical; Name=Segment S5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 273..281
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT INTRAMEM 282..302
FT /note="Pore-forming"
FT /evidence="ECO:0000255"
FT TOPO_DOM 303..304
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 305..325
FT /note="Helical; Name=Segment S6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 326..1230
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 475..596
FT /note="RCK N-terminal"
FT REGION 1..37
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 660..689
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1048..1078
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1204..1230
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 133
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 137
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 1..66
FT /note="MARAKLPRSPSEGKAGPGGAPAGAAAPEEPHGLSPLLPARGGGSVGSDVGQR
FT LPVEDFSLDSSLSQ -> MPLPDGARTPGGVCREARGGGYTNRTFEFDDGQCAPRRPCA
FT GDGALLDTAGFKMSDLDSEVLPLPPRYRFRDLLLGDPSFQNDDR (in isoform 2
FT and isoform 3)"
FT /evidence="ECO:0000303|PubMed:10718198,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_015470"
FT VAR_SEQ 1..66
FT /note="MARAKLPRSPSEGKAGPGGAPAGAAAPEEPHGLSPLLPARGGGSVGSDVGQR
FT LPVEDFSLDSSLSQ -> MPLPDGARTPGGVCREARGGGYTNRTFEFDDGQCAPR (in
FT isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_055700"
FT VAR_SEQ 266
FT /note="G -> GGCR (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_055701"
FT VAR_SEQ 1033
FT /note="E -> EPHDLRAQ (in isoform 2, isoform 3 and isoform
FT 4)"
FT /evidence="ECO:0000303|PubMed:10718198,
FT ECO:0000303|PubMed:14702039, ECO:0000303|PubMed:15489334"
FT /id="VSP_015471"
FT VAR_SEQ 1142..1162
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_044476"
FT VARIANT 269
FT /note="G -> S (in DEE14; dbSNP:rs587777264)"
FT /evidence="ECO:0000269|PubMed:24029078,
FT ECO:0000269|PubMed:26993267"
FT /id="VAR_078683"
FT VARIANT 379
FT /note="R -> Q (in ENFL5; dbSNP:rs397515407)"
FT /evidence="ECO:0000269|PubMed:23086396"
FT /id="VAR_069311"
FT VARIANT 409
FT /note="R -> Q (in DEE14; gain-of-function mutation;
FT dbSNP:rs397515402)"
FT /evidence="ECO:0000269|PubMed:23086397"
FT /id="VAR_069312"
FT VARIANT 455
FT /note="R -> H (in DEE14; dbSNP:rs397515404)"
FT /evidence="ECO:0000269|PubMed:23086397"
FT /id="VAR_069313"
FT VARIANT 497
FT /note="M -> V (in DEE14; dbSNP:rs886041691)"
FT /evidence="ECO:0000269|PubMed:27864847"
FT /id="VAR_078214"
FT VARIANT 562
FT /note="T -> I (in DEE14; unknown pathological significance;
FT dbSNP:rs1185192267)"
FT /evidence="ECO:0000269|PubMed:23708187"
FT /id="VAR_078641"
FT VARIANT 741
FT /note="I -> M (in DEE14; dbSNP:rs370521183)"
FT /evidence="ECO:0000269|PubMed:23086397"
FT /id="VAR_069314"
FT VARIANT 777
FT /note="Y -> H (in ENFL5; dbSNP:rs397515406)"
FT /evidence="ECO:0000269|PubMed:23086396"
FT /id="VAR_069315"
FT VARIANT 877
FT /note="M -> I (in ENFL5; dbSNP:rs797044544)"
FT /evidence="ECO:0000269|PubMed:23086396"
FT /id="VAR_069316"
FT VARIANT 877
FT /note="M -> K (in DEE14; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:26993267"
FT /id="VAR_078684"
FT VARIANT 909
FT /note="R -> C (in ENFL5; dbSNP:rs397515405)"
FT /evidence="ECO:0000269|PubMed:23086396"
FT /id="VAR_069317"
FT VARIANT 915
FT /note="A -> T (in DEE14; gain-of-function mutation;
FT dbSNP:rs397515403)"
FT /evidence="ECO:0000269|PubMed:23086397,
FT ECO:0000269|PubMed:26993267"
FT /id="VAR_069318"
FT VARIANT 928
FT /note="K -> E (in DEE14; dbSNP:rs1057519544)"
FT /evidence="ECO:0000269|PubMed:27864847"
FT /id="VAR_078215"
FT VARIANT 947
FT /note="A -> T (in DEE14; variant homologue in rat has
FT increased channel activity upon positive potentials;
FT dbSNP:rs1424788778)"
FT /evidence="ECO:0000269|PubMed:24463883"
FT /id="VAR_078685"
FT VARIANT 1088
FT /note="R -> Q (in DEE14; unknown pathological significance;
FT dbSNP:rs758311066)"
FT /evidence="ECO:0000269|PubMed:23708187"
FT /id="VAR_078642"
FT CONFLICT 107
FT /note="T -> I (in Ref. 1; BAG54469)"
FT /evidence="ECO:0000305"
FT CONFLICT 498
FT /note="L -> P (in Ref. 1; BAG54469)"
FT /evidence="ECO:0000305"
FT CONFLICT 615
FT /note="A -> V (in Ref. 4; AAI71770)"
FT /evidence="ECO:0000305"
FT CONFLICT 822
FT /note="K -> E (in Ref. 1; BAG54469)"
FT /evidence="ECO:0000305"
FT CONFLICT 969
FT /note="M -> K (in Ref. 1; BAG54469)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1230 AA; 138343 MW; 482D70015434493E CRC64;
MARAKLPRSP SEGKAGPGGA PAGAAAPEEP HGLSPLLPAR GGGSVGSDVG QRLPVEDFSL
DSSLSQVQVE FYVNENTFKE RLKLFFIKNQ RSSLRIRLFN FSLKLLTCLL YIVRVLLDDP
ALGIGCWGCP KQNYSFNDSS SEINWAPILW VERKMTLWAI QVIVAIISFL ETMLLIYLSY
KGNIWEQIFR VSFVLEMINT LPFIITIFWP PLRNLFIPVF LNCWLAKHAL ENMINDFHRA
ILRTQSAMFN QVLILFCTLL CLVFTGTCGI QHLERAGENL SLLTSFYFCI VTFSTVGYGD
VTPKIWPSQL LVVIMICVAL VVLPLQFEEL VYLWMERQKS GGNYSRHRAQ TEKHVVLCVS
SLKIDLLMDF LNEFYAHPRL QDYYVVILCP TEMDVQVRRV LQIPLWSQRV IYLQGSALKD
QDLMRAKMDN GEACFILSSR NEVDRTAADH QTILRAWAVK DFAPNCPLYV QILKPENKFH
VKFADHVVCE EECKYAMLAL NCICPATSTL ITLLVHTSRG QEGQESPEQW QRMYGRCSGN
EVYHIRMGDS KFFREYEGKS FTYAAFHAHK KYGVCLIGLK REDNKSILLN PGPRHILAAS
DTCFYINITK EENSAFIFKQ EEKRKKRAFS GQGLHEGPAR LPVHSIIASM GTVAMDLQGT
EHRPTQSGGG GGGSKLALPT ENGSGSRRPS IAPVLELADS SALLPCDLLS DQSEDEVTPS
DDEGLSVVEY VKGYPPNSPY IGSSPTLCHL LPVKAPFCCL RLDKGCKHNS YEDAKAYGFK
NKLIIVSAET AGNGLYNFIV PLRAYYRSRK ELNPIVLLLD NKPDHHFLEA ICCFPMVYYM
EGSVDNLDSL LQCGIIYADN LVVVDKESTM SAEEDYMADA KTIVNVQTMF RLFPSLSITT
ELTHPSNMRF MQFRAKDSYS LALSKLEKRE RENGSNLAFM FRLPFAAGRV FSISMLDTLL
YQSFVKDYMI TITRLLLGLD TTPGSGYLCA MKITEGDLWI RTYGRLFQKL CSSSAEIPIG
IYRTESHVFS TSESQISVNV EDCEDTREVK GPWGSRAGTG GSSQGRHTGG GDPAEHPLLR
RKSLQWARRL SRKAPKQAGR AAAAEWISQQ RLSLYRRSER QELSELVKNR MKHLGLPTTG
YEDVANLTAS DVMNRVNLGY LQDEMNDHQN TLSYVLINPP PDTRLEPSDI VYLIRSDPLA
HVASSSQSRK SSCSHKLSSC NPETRDETQL
