ID KCNT2_HUMAN Reviewed; 1135 AA. AC Q6UVM3; Q3SY59; Q5VTN1; Q6ZMT3; DT 04-DEC-2007, integrated into UniProtKB/Swiss-Prot. DT 05-JUL-2004, sequence version 1. DT 02-SEP-2026, entry version 174. DE RecName: Full=Potassium channel subfamily T member 2; DE AltName: Full=KNa1.2 {ECO:0000312|HGNC:HGNC:18866}; DE AltName: Full=Sequence like an intermediate conductance potassium channel subunit; DE AltName: Full=Sodium and chloride-activated ATP-sensitive potassium channel Slo2.1; GN Name=KCNT2; Synonyms=SLICK {ECO:0000303|PubMed:14684870}, Slo2.1; 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] (ISOFORM 1), FUNCTION, TRANSPORTER ACTIVITY, RP ACTIVITY REGULATION, AND TISSUE SPECIFICITY. RX PubMed=14684870; DOI=10.1523/jneurosci.23-37-11681.2003; RA Bhattacharjee A., Joiner W.J., Wu M., Yang Y., Sigworth F.J., RA Kaczmarek L.K.; RT "Slick (Slo2.1), a rapidly-gating sodium-activated potassium channel RT inhibited by ATP."; RL J. Neurosci. 23:11681-11691(2003). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4). RC TISSUE=Trachea; 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 [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Adipose tissue; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 4). 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 [6] RP FUNCTION, TRANSPORTER ACTIVITY, PHOSPHORYLATION, AND ACTIVITY REGULATION. RX PubMed=16687497; DOI=10.1523/jneurosci.3372-05.2006; RA Santi C.M., Ferreira G., Yang B., Gazula V.R., Butler A., Wei A., RA Kaczmarek L.K., Salkoff L.; RT "Opposite regulation of Slick and Slack K+ channels by neuromodulators."; RL J. Neurosci. 26:5059-5068(2006). RN [7] RP FUNCTION, ACTIVITY REGULATION, AND MUTAGENESIS OF LYS-1031. RX PubMed=25214519; DOI=10.14814/phy2.12118; RA Garg P., Sanguinetti M.C.; RT "Intracellular ATP does not inhibit Slo2.1 K+ channels."; RL Physiol. Rep. 2:0-0(2014). RN [8] RP FUNCTION, AND MUTAGENESIS OF LEU-267; LEU-270 AND MET-282. RX PubMed=27682982; DOI=10.1113/jp273225; RA Giese M.H., Gardner A., Hansen A., Sanguinetti M.C.; RT "Molecular mechanisms of Slo2 K+ channel closure."; RL J. Physiol. (Lond.) 595:2321-2336(2017). RN [9] RP FUNCTION, ACTIVITY REGULATION, TRANSPORTER ACTIVITY, SUBCELLULAR LOCATION, RP INVOLVEMENT IN DEE57, VARIANT DEE57 LEU-240, AND CHARACTERIZATION OF RP VARIANT DEE57 LEU-240. RX PubMed=29069600; DOI=10.1016/j.celrep.2017.09.088; RA Gururaj S., Palmer E.E., Sheehan G.D., Kandula T., Macintosh R., Ying K., RA Morris P., Tao J., Dias K.R., Zhu Y., Dinger M.E., Cowley M.J., Kirk E.P., RA Roscioli T., Sachdev R., Duffey M.E., Bye A., Bhattacharjee A.; RT "A De Novo Mutation in the Sodium-Activated Potassium Channel KCNT2 Alters RT Ion Selectivity and Causes Epileptic Encephalopathy."; RL Cell Rep. 21:926-933(2017). RN [10] RP VARIANTS DEE57 HIS-190 AND PRO-190, AND FUNCTION. RX PubMed=29740868; DOI=10.1002/ana.25248; RA Ambrosino P., Soldovieri M.V., Bast T., Turnpenny P.D., Uhrig S., RA Biskup S., Doecker M., Fleck T., Mosca I., Manocchio L., Iraci N., RA Taglialatela M., Lemke J.R.; RT "De novo gain-of-function variants in KCNT2 as a novel cause of RT developmental and epileptic encephalopathy."; RL Ann. Neurol. 83:1198-1204(2018). RN [11] RP VARIANT [LARGE SCALE ANALYSIS] ILE-33. RX PubMed=16959974; DOI=10.1126/science.1133427; RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V., RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., RA Velculescu V.E.; RT "The consensus coding sequences of human breast and colorectal cancers."; RL Science 314:268-274(2006). CC -!- FUNCTION: Sodium-activated and chloride-activated potassium channel CC (PubMed:14684870, PubMed:16687497, PubMed:25214519, PubMed:27682982, CC PubMed:29069600, PubMed:29740868). Produces rapidly activating outward CC rectifier K(+) currents (PubMed:14684870). Contributes to regulate CC neuronal excitability (PubMed:29069600). {ECO:0000269|PubMed:14684870, CC ECO:0000269|PubMed:16687497, ECO:0000269|PubMed:25214519, CC ECO:0000269|PubMed:27682982, ECO:0000269|PubMed:29069600, CC ECO:0000269|PubMed:29740868}. CC -!- CATALYTIC ACTIVITY: CC Reaction=K(+)(in) = K(+)(out); Xref=Rhea:RHEA:29463, ChEBI:CHEBI:29103; CC Evidence={ECO:0000269|PubMed:14684870, ECO:0000269|PubMed:29069600}; CC -!- ACTIVITY REGULATION: Are normally in a closed state unless activated by CC an increase in intracellular Na(+) and Cl(-) (PubMed:14684870, CC PubMed:16687497, PubMed:29069600). Inhibited upon stimulation of G CC protein-coupled receptors, such as CHRM1 and GRM1 (PubMed:16687497). CC There is conflicting data about the effect of ATP on KNCT2 channels CC activity. Intracellular ATP was initially report to inhibit the channel CC activity (PubMed:14684870). However, others studies conclude that KNCT2 CC channels are not inhibited by intracellular ATP (PubMed:25214519). CC {ECO:0000269|PubMed:14684870, ECO:0000269|PubMed:16687497, CC ECO:0000269|PubMed:25214519, ECO:0000269|PubMed:29069600}. CC -!- SUBUNIT: Homotetramer (By similarity). Forms heteromeric channels with CC KCNT1; these heterodimer channels differ from the homomers in their CC unitary conductance, kinetic behavior, subcellular localization, and CC response to activation of protein kinase C (By similarity). CC {ECO:0000250|UniProtKB:Q5JUK3, ECO:0000250|UniProtKB:Q6UVM4}. CC -!- INTERACTION: CC Q6UVM3; Q99767: APBA2; NbExp=2; IntAct=EBI-27012016, EBI-81711; CC Q6UVM3; Q12959: DLG1; NbExp=3; IntAct=EBI-27012016, EBI-357481; CC Q6UVM3; Q15700: DLG2; NbExp=2; IntAct=EBI-27012016, EBI-80426; CC Q6UVM3; Q92796: DLG3; NbExp=3; IntAct=EBI-27012016, EBI-80440; CC Q6UVM3; P78352: DLG4; NbExp=2; IntAct=EBI-27012016, EBI-80389; CC Q6UVM3; Q68DX3: FRMPD2; NbExp=3; IntAct=EBI-27012016, EBI-53993476; CC Q6UVM3; A4D2P6: GRID2IP; NbExp=2; IntAct=EBI-27012016, EBI-15893226; CC Q6UVM3; Q9Y3R0: GRIP1; NbExp=5; IntAct=EBI-27012016, EBI-5349621; CC Q6UVM3; Q9C0E4: GRIP2; NbExp=5; IntAct=EBI-27012016, EBI-949557; CC Q6UVM3; Q14005: IL16; NbExp=3; IntAct=EBI-27012016, EBI-2831580; CC Q6UVM3; Q8TBB1: LNX1; NbExp=3; IntAct=EBI-27012016, EBI-739832; CC Q6UVM3; Q8N448: LNX2; NbExp=2; IntAct=EBI-27012016, EBI-2340947; CC Q6UVM3; Q96QZ7: MAGI1; NbExp=2; IntAct=EBI-27012016, EBI-924464; CC Q6UVM3; Q86UL8: MAGI2; NbExp=5; IntAct=EBI-27012016, EBI-311035; CC Q6UVM3; Q6P0Q8: MAST2; NbExp=3; IntAct=EBI-27012016, EBI-493777; CC Q6UVM3; O75970: MPDZ; NbExp=3; IntAct=EBI-27012016, EBI-821405; CC Q6UVM3; Q86UT5: NHERF4; NbExp=2; IntAct=EBI-27012016, EBI-8744528; CC Q6UVM3; Q8NI35: PATJ; NbExp=9; IntAct=EBI-27012016, EBI-724390; CC Q6UVM3; Q5T2W1: PDZK1; NbExp=3; IntAct=EBI-27012016, EBI-349819; CC Q6UVM3; Q6ZMN7: PDZRN4; NbExp=3; IntAct=EBI-27012016, EBI-1222628; CC Q6UVM3; Q14160: SCRIB; NbExp=4; IntAct=EBI-27012016, EBI-357345; CC Q6UVM3; Q07157: TJP1; NbExp=2; IntAct=EBI-27012016, EBI-79553; CC Q6UVM3; Q9P202: WHRN; NbExp=2; IntAct=EBI-27012016, EBI-310886; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:29069600}; CC Multi-pass membrane protein {ECO:0000255}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=1; CC IsoId=Q6UVM3-1; Sequence=Displayed; CC Name=2; CC IsoId=Q6UVM3-2; Sequence=VSP_029855; CC Name=3; CC IsoId=Q6UVM3-3; Sequence=VSP_029854, VSP_029855, VSP_029856; CC Name=4; CC IsoId=Q6UVM3-4; Sequence=VSP_029852, VSP_029853, VSP_029855, CC VSP_029856, VSP_029857; CC -!- DOMAIN: The consensus ATP binding site (1025-GPKHSGKT-1032) seems to be CC non-functional. {ECO:0000269|PubMed:25214519}. CC -!- PTM: Phosphorylated by protein kinase C. Phosphorylation of the C- CC terminal domain inhibits channel activity. CC {ECO:0000269|PubMed:16687497}. CC -!- DISEASE: Developmental and epileptic encephalopathy 57 (DEE57) CC [MIM:617771]: A form of epileptic encephalopathy, a heterogeneous group CC of severe early-onset epilepsies characterized by refractory seizures, CC neurodevelopmental impairment, and poor prognosis. Development is CC normal prior to seizure onset, after which cognitive and motor delays CC become apparent. DEE57 is an autosomal dominant condition. CC {ECO:0000269|PubMed:29069600, ECO:0000269|PubMed:29740868}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- SIMILARITY: Belongs to the potassium channel family. Calcium-activated CC (TC 1.A.1.3) subfamily. KCa4.2/KCNT2 sub-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; AY359444; AAR06170.1; -; mRNA. DR EMBL; AK131498; BAD18642.1; -; mRNA. DR EMBL; BX647852; CAI46099.1; -; mRNA. DR EMBL; AL138931; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL139137; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL358853; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL591604; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC103948; AAI03949.1; -; mRNA. DR EMBL; BC103949; AAI03950.1; -; mRNA. DR EMBL; BC103950; AAI03951.1; -; mRNA. DR CCDS; CCDS1384.1; -. [Q6UVM3-1] DR CCDS; CCDS72994.1; -. [Q6UVM3-3] DR CCDS; CCDS72995.1; -. [Q6UVM3-2] DR RefSeq; NP_001274748.1; NM_001287819.3. [Q6UVM3-2] DR RefSeq; NP_001274749.1; NM_001287820.3. [Q6UVM3-3] DR RefSeq; NP_940905.2; NM_198503.5. [Q6UVM3-1] DR AlphaFoldDB; Q6UVM3; -. DR SMR; Q6UVM3; -. DR BioGRID; 131252; 32. DR FunCoup; Q6UVM3; 829. DR IntAct; Q6UVM3; 107. DR STRING; 9606.ENSP00000294725; -. DR BindingDB; Q6UVM3; -. DR ChEMBL; CHEMBL4739693; -. DR DrugBank; DB17045; Phorbol 12-myristate 13-acetate diester. DR DrugBank; DB08837; Tetraethylammonium. DR DrugCentral; Q6UVM3; -. DR GuidetoPHARMACOLOGY; 386; -. DR TCDB; 1.A.1.3.6; the voltage-gated ion channel (vic) superfamily. DR GlyCosmos; Q6UVM3; 1 site, No reported glycans. DR GlyGen; Q6UVM3; 1 site. DR iPTMnet; Q6UVM3; -. DR PhosphoSitePlus; Q6UVM3; -. DR BioMuta; KCNT2; -. DR DMDM; 74749370; -. DR jPOST; Q6UVM3; -. DR MassIVE; Q6UVM3; -. DR PaxDb; 9606-ENSP00000294725; -. DR PeptideAtlas; Q6UVM3; -. DR ProteomicsDB; 67432; -. [Q6UVM3-1] DR ProteomicsDB; 67433; -. [Q6UVM3-2] DR ProteomicsDB; 67434; -. [Q6UVM3-3] DR ProteomicsDB; 67435; -. [Q6UVM3-4] DR Antibodypedia; 34469; 176 antibodies from 22 providers. DR DNASU; 343450; -. DR Ensembl; ENST00000294725.14; ENSP00000294725.8; ENSG00000162687.19. [Q6UVM3-1] DR Ensembl; ENST00000367433.9; ENSP00000356403.5; ENSG00000162687.19. [Q6UVM3-2] DR Ensembl; ENST00000609185.5; ENSP00000476657.1; ENSG00000162687.19. [Q6UVM3-3] DR Ensembl; ENST00000709528.1; ENSP00000517744.1; ENSG00000291999.1. [Q6UVM3-2] DR Ensembl; ENST00000709531.1; ENSP00000517746.1; ENSG00000291999.1. [Q6UVM3-3] DR Ensembl; ENST00000709532.1; ENSP00000517747.1; ENSG00000291999.1. [Q6UVM3-1] DR GeneID; 343450; -. DR KEGG; hsa:343450; -. DR MANE-Select; ENST00000294725.14; ENSP00000294725.8; NM_198503.5; NP_940905.2. DR UCSC; uc001gtd.3; human. [Q6UVM3-1] DR AGR; HGNC:18866; -. DR ClinPGx; PA38726; -. DR CTD; 343450; -. DR DisGeNET; 343450; -. DR GeneCards; KCNT2; -. DR HGNC; HGNC:18866; KCNT2. DR HPA; ENSG00000162687; Tissue enhanced (ovary). DR MalaCards; KCNT2; -. DR MIM; 610044; gene. DR MIM; 617771; phenotype. DR OpenTargets; ENSG00000162687; -. DR VEuPathDB; HostDB:ENSG00000162687; -. DR eggNOG; KOG3193; Eukaryota. DR GeneTree; ENSGT00940000158746; -. DR HOGENOM; CLU_003370_0_0_1; -. DR InParanoid; Q6UVM3; -. DR OMA; SDVHPTY; -. DR OrthoDB; 257992at2759; -. DR PAN-GO; Q6UVM3; 4 GO annotations based on evolutionary models. DR PhylomeDB; Q6UVM3; -. DR PathwayCommons; Q6UVM3; -. DR SignaLink; Q6UVM3; -. DR Agora; ENSG00000162687; -. DR BioGRID-ORCS; 343450; 10 hits in 1143 CRISPR screens. DR ChiTaRS; KCNT2; human. DR GeneWiki; KCNT2; -. DR GenomeRNAi; 343450; -. DR Pharos; Q6UVM3; Tchem. DR PRO; PR:Q6UVM3; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; Q6UVM3; protein. DR Bgee; ENSG00000162687; Expressed in parietal pleura and 145 other cell types or tissues. DR ExpressionAtlas; Q6UVM3; baseline and differential. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0070089; F:chloride-activated potassium channel activity; IDA:UniProtKB. DR GO; GO:0005228; F:intracellular sodium-activated potassium channel activity; IDA:UniProtKB. DR GO; GO:0015271; F:outward rectifier potassium channel activity; IBA:GO_Central. DR GO; GO:0097623; P:potassium ion export across plasma membrane; IDA:UniProtKB. DR GO; GO:0071805; P:potassium ion transmembrane transport; IBA:GO_Central. DR FunFam; 3.40.50.720:FF:000011; Potassium channel subfamily T member 1; 1. DR FunFam; 3.40.50.720:FF:000034; Potassium channel subfamily T member 1; 1. DR FunFam; 1.10.287.70:FF:000069; Potassium sodium-activated channel subfamily T member 1; 1. DR Gene3D; 1.10.287.70; -; 1. DR Gene3D; 3.40.50.720; NAD(P)-binding Rossmann-like Domain; 2. DR InterPro; IPR003929; K_chnl_BK_asu. DR InterPro; IPR013099; K_chnl_dom. DR InterPro; IPR047871; K_chnl_Slo-like. DR InterPro; IPR036291; NAD(P)-bd_dom_sf. DR InterPro; IPR003148; RCK_N. DR PANTHER; PTHR10027; CALCIUM-ACTIVATED POTASSIUM CHANNEL ALPHA CHAIN; 1. DR PANTHER; PTHR10027:SF9; POTASSIUM CHANNEL SUBFAMILY T MEMBER 2; 1. DR Pfam; PF03493; BK_channel_a; 1. DR Pfam; PF07885; Ion_trans_2; 1. DR Pfam; PF22614; Slo-like_RCK; 2. DR SUPFAM; SSF51735; NAD(P)-binding Rossmann-fold domains; 1. DR SUPFAM; SSF81324; Voltage-gated potassium channels; 1. DR PROSITE; PS51201; RCK_N; 2. PE 1: Evidence at protein level; KW Alternative splicing; Cell membrane; Disease variant; Epilepsy; KW Glycoprotein; Ion channel; Ion transport; Membrane; Phosphoprotein; KW Potassium; Potassium channel; Potassium transport; KW Proteomics identification; Reference proteome; Transmembrane; KW Transmembrane helix; Transport. FT CHAIN 1..1135 FT /note="Potassium channel subfamily T member 2" FT /id="PRO_0000312503" FT TOPO_DOM 1..63 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 64..84 FT /note="Helical; Name=Segment S1" FT /evidence="ECO:0000255" FT TOPO_DOM 85..101 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 102..122 FT /note="Helical; Name=Segment S2" FT /evidence="ECO:0000255" FT TOPO_DOM 123..137 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 138..158 FT /note="Helical; Name=Segment S3" FT /evidence="ECO:0000255" FT TOPO_DOM 159..164 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 165..185 FT /note="Helical; Name=Segment S4" FT /evidence="ECO:0000255" FT TOPO_DOM 186..198 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 199..219 FT /note="Helical; Name=Segment S5" FT /evidence="ECO:0000255" FT TOPO_DOM 220..228 FT /note="Extracellular" FT /evidence="ECO:0000255" FT INTRAMEM 229..249 FT /note="Pore-forming" FT /evidence="ECO:0000255" FT TOPO_DOM 250..256 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 257..277 FT /note="Helical; Name=Segment S6" FT /evidence="ECO:0000255" FT TOPO_DOM 278..1135 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT DOMAIN 299..435 FT /note="RCK N-terminal 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00543" FT DOMAIN 718..858 FT /note="RCK N-terminal 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00543" FT REGION 977..1010 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1017..1036 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1113..1135 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1017..1030 FT /note="Basic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1118..1127 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT CARBOHYD 99 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT VAR_SEQ 129..153 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15489334" FT /id="VSP_029852" FT VAR_SEQ 468 FT /note="Q -> QCVCLCCR (in isoform 4)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15489334" FT /id="VSP_029853" FT VAR_SEQ 469..518 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000305" FT /id="VSP_029854" FT VAR_SEQ 760..783 FT /note="Missing (in isoform 2, isoform 3 and isoform 4)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:17974005" FT /id="VSP_029855" FT VAR_SEQ 970 FT /note="E -> ESRKIASQ (in isoform 3 and isoform 4)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15489334" FT /id="VSP_029856" FT VAR_SEQ 1071..1135 FT /note="DEMNDHQSTLSYILINPSPDTRIELNDVVYLIRPDPLAYLPNSEPSRRNSIC FT NVTGQDSREETQL -> GMLFKNYCIYGLVISCH (in isoform 4)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15489334" FT /id="VSP_029857" FT VARIANT 33 FT /note="V -> I (in a breast cancer sample; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:16959974" FT /id="VAR_037527" FT VARIANT 190 FT /note="R -> H (in DEE57; markedly increased outward FT rectifying current)" FT /evidence="ECO:0000269|PubMed:29740868" FT /id="VAR_089251" FT VARIANT 190 FT /note="R -> P (in DEE57; markedly increased outward FT rectifying current)" FT /evidence="ECO:0000269|PubMed:29740868" FT /id="VAR_089252" FT VARIANT 240 FT /note="F -> L (in DEE57; decreased protein abundance; loss FT of chloride-activated potassium channel activity; loss of FT potassium selectivity. Causes membrane hyperexcitability in FT primary neurons; dbSNP:rs1060499537)" FT /evidence="ECO:0000269|PubMed:29069600" FT /id="VAR_080867" FT VARIANT 413 FT /note="C -> W (in dbSNP:rs12738104)" FT /id="VAR_037528" FT VARIANT 429 FT /note="K -> N (in dbSNP:rs12742082)" FT /id="VAR_037529" FT MUTAGEN 267 FT /note="L->H,N,T,E,Q,S: Constitutively open channel." FT /evidence="ECO:0000269|PubMed:27682982" FT MUTAGEN 267 FT /note="L->N: Constitutively open channel; when associated FT with N-270." FT /evidence="ECO:0000269|PubMed:27682982" FT MUTAGEN 270 FT /note="L->N: Does not affect channel activity. FT Constitutively open channel; when associated with N-267." FT /evidence="ECO:0000269|PubMed:27682982" FT MUTAGEN 270 FT /note="L->W,H,Q: Constitutively open channel." FT /evidence="ECO:0000269|PubMed:27682982" FT MUTAGEN 282 FT /note="M->A: Does not induce constitutive opening." FT /evidence="ECO:0000269|PubMed:27682982" FT MUTAGEN 1031 FT /note="K->A: Does not affect KCNT2 channel activity." FT /evidence="ECO:0000269|PubMed:25214519" SQ SEQUENCE 1135 AA; 130501 MW; 4957C6DAB1E030CF CRC64; MVDLESEVPP LPPRYRFRDL LLGDQGWQND DRVQVEFYMN ENTFKERLKL FFIKNQRSSL RIRLFNFSLK LLSCLLYIIR VLLENPSQGN EWSHIFWVNR SLPLWGLQVS VALISLFETI LLGYLSYKGN IWEQILRIPF ILEIINAVPF IISIFWPSLR NLFVPVFLNC WLAKHALENM INDLHRAIQR TQSAMFNQVL ILISTLLCLI FTCICGIQHL ERIGKKLNLF DSLYFCIVTF STVGFGDVTP ETWSSKLFVV AMICVALVVL PIQFEQLAYL WMERQKSGGN YSRHRAQTEK HVVLCVSSLK IDLLMDFLNE FYAHPRLQDY YVVILCPTEM DVQVRRVLQI PMWSQRVIYL QGSALKDQDL LRAKMDDAEA CFILSSRCEV DRTSSDHQTI LRAWAVKDFA PNCPLYVQIL KPENKFHIKF ADHVVCEEEF KYAMLALNCI CPATSTLITL LVHTSRGQEG QQSPEQWQKM YGRCSGNEVY HIVLEESTFF AEYEGKSFTY ASFHAHKKFG VCLIGVRRED NKNILLNPGP RYIMNSTDIC FYINITKEEN SAFKNQDQQR KSNVSRSFYH GPSRLPVHSI IASMGTVAID LQDTSCRSAS GPTLSLPTEG SKEIRRPSIA PVLEVADTSS IQTCDLLSDQ SEDETTPDEE MSSNLEYAKG YPPYSPYIGS SPTFCHLLHE KVPFCCLRLD KSCQHNYYED AKAYGFKNKL IIVAAETAGN GLYNFIVPLR AYYRPKKELN PIVLLLDNPP DMHFLDAICW FPMVYYMVGS IDNLDDLLRC GVTFAANMVV VDKESTMSAE EDYMADAKTI VNVQTLFRLF SSLSIITELT HPANMRFMQF RAKDCYSLAL SKLEKKERER GSNLAFMFRL PFAAGRVFSI SMLDTLLYQS FVKDYMISIT RLLLGLDTTP GSGFLCSMKI TADDLWIRTY ARLYQKLCSS TGDVPIGIYR TESQKLTTSE SQISISVEEW EDTKDSKEQG HHRSNHRNST SSDQSDHPLL RRKSMQWARR LSRKGPKHSG KTAEKITQQR LNLYRRSERQ ELAELVKNRM KHLGLSTVGY DEMNDHQSTL SYILINPSPD TRIELNDVVY LIRPDPLAYL PNSEPSRRNS ICNVTGQDSR EETQL //