ID KCNQ3_HUMAN Reviewed; 872 AA. AC O43525; A2VCT8; B4DJY4; E7EQ89; DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot. DT 15-JUL-1999, sequence version 2. DT 13-SEP-2023, entry version 206. DE RecName: Full=Potassium voltage-gated channel subfamily KQT member 3 {ECO:0000305}; DE AltName: Full=KQT-like 3; DE AltName: Full=Potassium channel subunit alpha KvLQT3; DE AltName: Full=Voltage-gated potassium channel subunit Kv7.3; GN Name=KCNQ3 {ECO:0000312|HGNC:HGNC:6297}; 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 [GENOMIC DNA], CHARACTERIZATION OF VARIANT BFNS2 RP VAL-310, MUTAGENESIS OF GLY-318, AND FUNCTION. RC TISSUE=Brain; RX PubMed=9872318; DOI=10.1038/25367; RA Schroeder B.C., Kubisch C., Stein V., Jentsch T.J.; RT "Moderate loss of function of cyclic-AMP-modulated KCNQ2/KCNQ3 K+ channels RT causes epilepsy."; RL Nature 396:687-690(1998). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND CHARACTERIZATION. RC TISSUE=Brain, and Fetal brain; RX PubMed=9677360; DOI=10.1074/jbc.273.31.19419; RA Yang W.-P., Levesque P.C., Little W.A., Conder M.L., Ramakrishnan P., RA Neubauer M.G., Blanar M.A.; RT "Functional expression of two KvLQT1-related potassium channels responsible RT for an inherited idiopathic epilepsy."; RL J. Biol. Chem. 273:19419-19423(1998). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Thalamus; 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 [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16421571; DOI=10.1038/nature04406; RA Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M., RA Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L., RA Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S., RA Asakawa T., Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A., RA Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III, RA Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., RA Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P., RA Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H., RA Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B., RA O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K., RA Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L., RA Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G., RA Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W., RA Platzer M., Shimizu N., Lander E.S.; RT "DNA sequence and analysis of human chromosome 8."; RL Nature 439:331-335(2006). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-7; 34-588 AND 601-872 (ISOFORM RP 1). 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 NUCLEOTIDE SEQUENCE [MRNA] OF 48-872 (ISOFORM 1), AND VARIANT BFNS2 RP VAL-310. RC TISSUE=Brain; RX PubMed=9425900; DOI=10.1038/ng0198-53; RA Charlier C., Singh N.A., Ryan S.G., Lewis T.B., Reus B.E., Leach R.J., RA Leppert M.; RT "A pore mutation in a novel KQT-like potassium channel gene in an RT idiopathic epilepsy family."; RL Nat. Genet. 18:53-55(1998). RN [7] RP INVOLVEMENT IN M-LIKE CURRENT. RX PubMed=10479678; DOI=10.1523/jneurosci.19-18-07742.1999; RA Selyanko A.A., Hadley J.K., Wood I.C., Abogadie F.C., Delmas P., RA Buckley N.J., London B., Brown D.A.; RT "Two types of K(+) channel subunit, Erg1 and KCNQ2/3, contribute to the M- RT like current in a mammalian neuronal cell."; RL J. Neurosci. 19:7742-7756(1999). RN [8] RP ASSOCIATION WITH KCNE2. RX PubMed=11034315; DOI=10.1016/s0014-5793(00)01918-9; RA Tinel N., Diochot S., Lauritzen I., Barhanin J., Lazdunski M., Borsotto M.; RT "M-type KCNQ2-KCNQ3 potassium channels are modulated by the KCNE2 RT subunit."; RL FEBS Lett. 480:137-141(2000). RN [9] RP SUBCELLULAR LOCATION. RX PubMed=10788442; DOI=10.1074/jbc.275.18.13343; RA Schwake M., Pusch M., Kharkovets T., Jentsch T.J.; RT "Surface expression and single channel properties of KCNQ2/KCNQ3, M-type K+ RT channels involved in epilepsy."; RL J. Biol. Chem. 275:13343-13348(2000). RN [10] RP INHIBITION BY M1 MUSCARINIC RECEPTORS. RX PubMed=10684873; DOI=10.1523/jneurosci.20-05-01710.2000; RA Shapiro M.S., Roche J.P., Kaftan E.J., Cruzblanca H., Mackie K., Hille B.; RT "Reconstitution of muscarinic modulation of the KCNQ2/KCNQ3 K(+) channels RT that underlie the neuronal M current."; RL J. Neurosci. 20:1710-1721(2000). RN [11] RP INHIBITION BY M1 MUSCARINIC RECEPTORS. RX PubMed=10713961; DOI=10.1111/j.1469-7793.2000.t01-2-00349.x; RA Selyanko A.A., Hadley J.K., Wood I.C., Abogadie F.C., Jentsch T.J., RA Brown D.A.; RT "Inhibition of KCNQ1-4 potassium channels expressed in mammalian cells via RT M1 muscarinic acetylcholine receptors."; RL J. Physiol. (Lond.) 522:349-355(2000). RN [12] RP ACTIVATION BY RETICABINE. RX PubMed=10908292; DOI=10.1124/mol.58.2.253; RA Main M.J., Cryan J.E., Dupere J.R., Cox B., Clare J.J., Burbidge S.A.; RT "Modulation of KCNQ2/3 potassium channels by the novel anticonvulsant RT retigabine."; RL Mol. Pharmacol. 58:253-262(2000). RN [13] RP ACTIVATION BY RETICABINE. RX PubMed=10953053; DOI=10.1124/mol.58.3.591; RA Wickenden A.D., Yu W., Zou A., Jegla T., Wagoner P.K.; RT "Retigabine, a novel anti-convulsant, enhances activation of KCNQ2/Q3 RT potassium channels."; RL Mol. Pharmacol. 58:591-600(2000). RN [14] RP ACTIVATION BY RETICABINE. RX PubMed=10713399; DOI=10.1016/s0304-3940(00)00866-1; RA Rundfeldt C., Netzer R.; RT "The novel anticonvulsant retigabine activates M-currents in Chinese RT hamster ovary-cells transfected with human KCNQ2/3 subunits."; RL Neurosci. Lett. 282:73-76(2000). RN [15] RP FUNCTION, SUBUNIT, AND ACTIVATION BY RETICABINE. RX PubMed=11159685; DOI=10.1038/sj.bjp.0703861; RA Wickenden A.D., Zou A., Wagoner P.K., Jegla T.; RT "Characterization of KCNQ5/Q3 potassium channels expressed in mammalian RT cells."; RL Br. J. Pharmacol. 132:381-384(2001). RN [16] RP FUNCTION, PHOSPHORYLATION AT THR-246, AND MUTAGENESIS OF THR-246. RX PubMed=16319223; DOI=10.1073/pnas.0509122102; RA Surti T.S., Huang L., Jan Y.N., Jan L.Y., Cooper E.C.; RT "Identification by mass spectrometry and functional characterization of two RT phosphorylation sites of KCNQ2/KCNQ3 channels."; RL Proc. Natl. Acad. Sci. U.S.A. 102:17828-17833(2005). RN [17] RP UBIQUITINATION BY NEDD4L. RX PubMed=27445338; DOI=10.1074/jbc.m116.722637; RA Anta B., Martin-Rodriguez C., Gomis-Perez C., Calvo L., Lopez-Benito S., RA Calderon-Garcia A.A., Vicente-Garcia C., Villarroel A., Arevalo J.C.; RT "Ubiquitin-specific Protease 36 (USP36) Controls Neuronal Precursor Cell- RT expressed Developmentally Down-regulated 4-2 (Nedd4-2) Actions over the RT Neurotrophin Receptor TrkA and Potassium Voltage-gated Channels 7.2/3 RT (Kv7.2/3)."; RL J. Biol. Chem. 291:19132-19145(2016). RN [18] RP FUNCTION. RX PubMed=28793216; DOI=10.1016/j.bpj.2017.06.055; RA Manville R.W., Neverisky D.L., Abbott G.W.; RT "SMIT1 Modifies KCNQ Channel Function and Pharmacology by Physical RT Interaction with the Pore."; RL Biophys. J. 113:613-626(2017). RN [19] {ECO:0007744|PDB:5J03} RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 354-409 IN COMPLEX WITH RP CALMODULIN, SUBUNIT, INTERACTION WITH CALMODULIN, AND REGION. RX PubMed=27564677; DOI=10.1021/acs.biochem.6b00477; RA Strulovich R., Tobelaim W.S., Attali B., Hirsch J.A.; RT "Structural insights into the M-channel proximal C-terminus/calmodulin RT complex."; RL Biochemistry 55:5353-5365(2016). RN [20] RP VARIANT BFNS2 ARG-309. RX PubMed=10852552; RX DOI=10.1002/1531-8249(200006)47:6<822::aid-ana19>3.3.co;2-o; RA Hirose S., Zenri F., Akiyoshi H., Fukuma G., Iwata H., Inoue T., RA Yonetani M., Tsutsumi M., Muranaka H., Kurokawa T., Hanai T., Wada K., RA Kaneko S., Mitsudome A.; RT "A novel mutation of KCNQ3 (c.925T-->C) in a Japanese family with benign RT familial neonatal convulsions."; RL Ann. Neurol. 47:822-826(2000). RN [21] RP VARIANTS BFNS2 GLY-305 AND VAL-310, CHARACTERIZATION OF VARIANT BFNS2 RP GLY-305, VARIANT SER-468, CHARACTERIZATION OF VARIANT SER-468, AND RP FUNCTION. RX PubMed=14534157; DOI=10.1093/brain/awg286; RG The BFNC physician consortium; RA Singh N.A., Westenskow P., Charlier C., Pappas C., Leslie J., Dillon J., RA Anderson V.E., Sanguinetti M.C., Leppert M.F.; RT "KCNQ2 and KCNQ3 potassium channel genes in benign familial neonatal RT convulsions: expansion of the functional and mutation spectrum."; RL Brain 126:2726-2737(2003). RN [22] RP VARIANT SER-574. RX PubMed=22612257; DOI=10.1111/j.1528-1167.2012.03516.x; RA Lemke J.R., Riesch E., Scheurenbrand T., Schubach M., Wilhelm C., RA Steiner I., Hansen J., Courage C., Gallati S., Buerki S., Strozzi S., RA Simonetti B.G., Grunt S., Steinlin M., Alber M., Wolff M., Klopstock T., RA Prott E.C., Lorenz R., Spaich C., Rona S., Lakshminarasimhan M., Kroell J., RA Dorn T., Kraemer G., Synofzik M., Becker F., Weber Y.G., Lerche H., RA Boehm D., Biskup S.; RT "Targeted next generation sequencing as a diagnostic tool in epileptic RT disorders."; RL Epilepsia 53:1387-1398(2012). RN [23] RP VARIANT CYS-780. RX PubMed=23360469; DOI=10.1111/epi.12089; RA Zara F., Specchio N., Striano P., Robbiano A., Gennaro E., Paravidino R., RA Vanni N., Beccaria F., Capovilla G., Bianchi A., Caffi L., Cardilli V., RA Darra F., Bernardina B.D., Fusco L., Gaggero R., Giordano L., Guerrini R., RA Incorpora G., Mastrangelo M., Spaccini L., Laverda A.M., Vecchi M., RA Vanadia F., Veggiotti P., Viri M., Occhi G., Budetta M., Taglialatela M., RA Coviello D.A., Vigevano F., Minetti C.; RT "Genetic testing in benign familial epilepsies of the first year of life: RT clinical and diagnostic significance."; RL Epilepsia 54:425-436(2013). RN [24] RP VARIANT BFNS2 VAL-340. RX PubMed=25982755; DOI=10.1111/epi.13020; RA Grinton B.E., Heron S.E., Pelekanos J.T., Zuberi S.M., Kivity S., Afawi Z., RA Williams T.C., Casalaz D.M., Yendle S., Linder I., Lev D., Lerman-Sagie T., RA Malone S., Bassan H., Goldberg-Stern H., Stanley T., Hayman M., Calvert S., RA Korczyn A.D., Shevell M., Scheffer I.E., Mulley J.C., Berkovic S.F.; RT "Familial neonatal seizures in 36 families: Clinical and genetic features RT correlate with outcome."; RL Epilepsia 56:1071-1080(2015). CC -!- FUNCTION: Associates with KCNQ2 or KCNQ5 to form a potassium channel CC with essentially identical properties to the channel underlying the CC native M-current, a slowly activating and deactivating potassium CC conductance which plays a critical role in determining the subthreshold CC electrical excitability of neurons as well as the responsiveness to CC synaptic inputs. Therefore, it is important in the regulation of CC neuronal excitability. KCNQ2-KCNQ3 channel is selectively permeable to CC other cations besides potassium, in decreasing order of affinity K(+) > CC Rb(+) > Cs(+) > Na(+). Associates with Na(+)-coupled myo-inositol CC symporter SLC5A3 forming a coregulatory complex that alters ion CC selectivity, increasing Na(+) and Cs(+) permeation relative to K(+) CC permeation (PubMed:28793216). {ECO:0000269|PubMed:11159685, CC ECO:0000269|PubMed:14534157, ECO:0000269|PubMed:16319223, CC ECO:0000269|PubMed:28793216, ECO:0000269|PubMed:9872318}. CC -!- SUBUNIT: Heterotetramer with KCNQ2; form the heterotetrameric M CC potassium channel (PubMed:27564677). Interacts with calmodulin; the CC interaction is calcium-independent, constitutive and participates in CC the proper assembly of a functional heterotetrameric M channel CC (PubMed:27564677). Heteromultimer with KCNQ5 (PubMed:11159685). May CC associate with KCNE2 (PubMed:11034315). Interacts with IQCJ-SCHIP1 (By CC similarity). Interacts (via the pore module) with SLC5A3; forms a CC coregulatory complex that alters ion selectivity, voltage dependence CC and gating kinetics of the channel. {ECO:0000250|UniProtKB:Q8K3F6, CC ECO:0000269|PubMed:11034315, ECO:0000269|PubMed:11159685, CC ECO:0000269|PubMed:27564677}. CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:10788442}; CC Multi-pass membrane protein {ECO:0000255}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=O43525-1; Sequence=Displayed; CC Name=2; CC IsoId=O43525-2; Sequence=VSP_044906, VSP_044907; CC -!- TISSUE SPECIFICITY: Predominantly expressed in brain. CC -!- DOMAIN: The segment S4 is probably the voltage-sensor and is CC characterized by a series of positively charged amino acids at every CC third position. {ECO:0000250}. CC -!- PTM: KCNQ2/KCNQ3 are ubiquitinated by NEDD4L. Ubiquitination leads to CC protein degradation (Probable). Degradation induced by NEDD4L is CC inhibited by USP36 (PubMed:27445338). {ECO:0000269|PubMed:27445338, CC ECO:0000305|PubMed:27445338}. CC -!- DISEASE: Seizures, benign familial neonatal 2 (BFNS2) [MIM:121201]: A CC disorder characterized by clusters of seizures occurring in the first CC days of life. Most patients have spontaneous remission by 12 months of CC age and show normal psychomotor development. The disorder is CC distinguished from benign familial infantile seizures by an earlier age CC at onset. {ECO:0000269|PubMed:10852552, ECO:0000269|PubMed:14534157, CC ECO:0000269|PubMed:25982755, ECO:0000269|PubMed:9425900, CC ECO:0000269|PubMed:9872318}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Note=Defects in KCNQ3 may be involved in epileptic disorders. CC These are characterized by paroxysmal transient disturbances of the CC electrical activity of the brain that may be manifested as episodic CC impairment or loss of consciousness, abnormal motor phenomena, psychic CC or sensory disturbances, or perturbation of the autonomic nervous CC system. {ECO:0000269|PubMed:22612257}. CC -!- SIMILARITY: Belongs to the potassium channel family. KQT (TC 1.A.1.15) CC subfamily. Kv7.3/KCNQ3 sub-subfamily. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAI28577.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC Sequence=AAI28577.1; Type=Miscellaneous discrepancy; Note=Aberrant splicing.; Evidence={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; AF071491; AAC96101.1; -; Genomic_DNA. DR EMBL; AF071478; AAC96101.1; JOINED; Genomic_DNA. DR EMBL; AF071479; AAC96101.1; JOINED; Genomic_DNA. DR EMBL; AF071480; AAC96101.1; JOINED; Genomic_DNA. DR EMBL; AF071481; AAC96101.1; JOINED; Genomic_DNA. DR EMBL; AF071482; AAC96101.1; JOINED; Genomic_DNA. DR EMBL; AF071483; AAC96101.1; JOINED; Genomic_DNA. DR EMBL; AF071484; AAC96101.1; JOINED; Genomic_DNA. DR EMBL; AF071485; AAC96101.1; JOINED; Genomic_DNA. DR EMBL; AF071486; AAC96101.1; JOINED; Genomic_DNA. DR EMBL; AF071487; AAC96101.1; JOINED; Genomic_DNA. DR EMBL; AF071488; AAC96101.1; JOINED; Genomic_DNA. DR EMBL; AF071489; AAC96101.1; JOINED; Genomic_DNA. DR EMBL; AF071490; AAC96101.1; JOINED; Genomic_DNA. DR EMBL; AK296293; BAG58996.1; -; mRNA. DR EMBL; AC018540; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC123776; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC131042; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC136373; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC128576; AAI28577.1; ALT_SEQ; mRNA. DR EMBL; AF033347; AAB97314.1; -; mRNA. DR CCDS; CCDS34943.1; -. [O43525-1] DR CCDS; CCDS56554.1; -. [O43525-2] DR RefSeq; NP_001191753.1; NM_001204824.1. [O43525-2] DR RefSeq; NP_004510.1; NM_004519.3. [O43525-1] DR PDB; 5J03; X-ray; 2.00 A; A=354-409. DR PDBsum; 5J03; -. DR AlphaFoldDB; O43525; -. DR SMR; O43525; -. DR BioGRID; 109987; 14. DR CORUM; O43525; -. DR STRING; 9606.ENSP00000373648; -. DR BindingDB; O43525; -. DR ChEMBL; CHEMBL2684; -. DR DrugBank; DB00321; Amitriptyline. DR DrugBank; DB00586; Diclofenac. DR DrugBank; DB00228; Enflurane. DR DrugBank; DB04953; Ezogabine. DR DrugBank; DB00996; Gabapentin. DR DrugBank; DB06089; ICA-105665. DR DrugBank; DB00939; Meclofenamic acid. DR DrugBank; DB01110; Miconazole. DR DrugBank; DB01069; Promethazine. DR DrugCentral; O43525; -. DR GuidetoPHARMACOLOGY; 562; -. DR TCDB; 1.A.1.15.3; the voltage-gated ion channel (vic) superfamily. DR GlyCosmos; O43525; 1 site, 1 glycan. DR GlyGen; O43525; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; O43525; -. DR PhosphoSitePlus; O43525; -. DR BioMuta; KCNQ3; -. DR jPOST; O43525; -. DR MassIVE; O43525; -. DR PaxDb; O43525; -. DR PeptideAtlas; O43525; -. DR ProteomicsDB; 17526; -. DR ProteomicsDB; 49030; -. [O43525-1] DR Antibodypedia; 14124; 181 antibodies from 24 providers. DR DNASU; 3786; -. DR Ensembl; ENST00000388996.10; ENSP00000373648.3; ENSG00000184156.17. [O43525-1] DR Ensembl; ENST00000521134.6; ENSP00000429799.1; ENSG00000184156.17. [O43525-2] DR GeneID; 3786; -. DR KEGG; hsa:3786; -. DR MANE-Select; ENST00000388996.10; ENSP00000373648.3; NM_004519.4; NP_004510.1. DR UCSC; uc003yti.4; human. [O43525-1] DR AGR; HGNC:6297; -. DR CTD; 3786; -. DR DisGeNET; 3786; -. DR GeneCards; KCNQ3; -. DR GeneReviews; KCNQ3; -. DR HGNC; HGNC:6297; KCNQ3. DR HPA; ENSG00000184156; Tissue enriched (brain). DR MalaCards; KCNQ3; -. DR MIM; 121201; phenotype. DR MIM; 602232; gene. DR neXtProt; NX_O43525; -. DR OpenTargets; ENSG00000184156; -. DR Orphanet; 306; Benign familial infantile epilepsy. DR Orphanet; 1949; Benign familial neonatal epilepsy. DR Orphanet; 307; Juvenile myoclonic epilepsy. DR PharmGKB; PA30075; -. DR VEuPathDB; HostDB:ENSG00000184156; -. DR eggNOG; KOG1419; Eukaryota. DR GeneTree; ENSGT00940000159760; -. DR InParanoid; O43525; -. DR OMA; QDRDDYM; -. DR OrthoDB; 2911641at2759; -. DR PhylomeDB; O43525; -. DR TreeFam; TF315186; -. DR PathwayCommons; O43525; -. DR Reactome; R-HSA-1296072; Voltage gated Potassium channels. DR Reactome; R-HSA-445095; Interaction between L1 and Ankyrins. DR SignaLink; O43525; -. DR SIGNOR; O43525; -. DR BioGRID-ORCS; 3786; 7 hits in 1151 CRISPR screens. DR ChiTaRS; KCNQ3; human. DR GeneWiki; KvLQT3; -. DR GenomeRNAi; 3786; -. DR Pharos; O43525; Tclin. DR PRO; PR:O43525; -. DR Proteomes; UP000005640; Chromosome 8. DR RNAct; O43525; Protein. DR Bgee; ENSG00000184156; Expressed in ganglionic eminence and 132 other tissues. DR ExpressionAtlas; O43525; baseline and differential. DR Genevisible; O43525; HS. DR GO; GO:0043194; C:axon initial segment; ISS:BHF-UCL. DR GO; GO:0009986; C:cell surface; IEA:Ensembl. DR GO; GO:0005739; C:mitochondrion; IEA:GOC. DR GO; GO:0033268; C:node of Ranvier; ISS:BHF-UCL. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0045202; C:synapse; IEA:GOC. DR GO; GO:0008076; C:voltage-gated potassium channel complex; IDA:UniProtKB. DR GO; GO:0005516; F:calmodulin binding; IDA:UniProtKB. DR GO; GO:0005249; F:voltage-gated potassium channel activity; IDA:UniProtKB. DR GO; GO:0099610; P:action potential initiation; IEA:Ensembl. DR GO; GO:0097314; P:apoptosome assembly; IEA:Ensembl. DR GO; GO:0071277; P:cellular response to calcium ion; IEA:Ensembl. DR GO; GO:0071466; P:cellular response to xenobiotic stimulus; IEA:Ensembl. DR GO; GO:0007268; P:chemical synaptic transmission; TAS:ProtInc. DR GO; GO:0098976; P:excitatory chemical synaptic transmission; IEA:Ensembl. DR GO; GO:0010467; P:gene expression; IEA:Ensembl. DR GO; GO:0098977; P:inhibitory chemical synaptic transmission; IEA:Ensembl. DR GO; GO:0060081; P:membrane hyperpolarization; IEA:Ensembl. DR GO; GO:0051882; P:mitochondrial depolarization; IEA:Ensembl. DR GO; GO:0021675; P:nerve development; IEA:Ensembl. DR GO; GO:0051402; P:neuron apoptotic process; IEA:Ensembl. DR GO; GO:0016322; P:neuron remodeling; IEA:Ensembl. DR GO; GO:0019228; P:neuronal action potential; IEA:Ensembl. DR GO; GO:0071805; P:potassium ion transmembrane transport; IDA:UniProtKB. DR GO; GO:0006606; P:protein import into nucleus; IEA:Ensembl. DR GO; GO:0006605; P:protein targeting; IEA:Ensembl. DR GO; GO:0036343; P:psychomotor behavior; IEA:Ensembl. DR GO; GO:0099611; P:regulation of action potential firing threshold; IEA:Ensembl. DR GO; GO:0034765; P:regulation of monoatomic ion transmembrane transport; IEA:UniProtKB-KW. DR GO; GO:0048167; P:regulation of synaptic plasticity; IEA:Ensembl. DR GO; GO:0010996; P:response to auditory stimulus; IEA:Ensembl. DR GO; GO:0014070; P:response to organic cyclic compound; IEA:Ensembl. DR GO; GO:0007605; P:sensory perception of sound; IEA:Ensembl. DR GO; GO:1903701; P:substantia propria of cornea development; IEA:Ensembl. DR Gene3D; 1.10.287.70; -; 1. DR Gene3D; 6.10.140.1910; -; 2. DR InterPro; IPR020969; Ankyrin-G_BS. DR InterPro; IPR005821; Ion_trans_dom. DR InterPro; IPR003937; K_chnl_volt-dep_KCNQ. DR InterPro; IPR003948; K_chnl_volt-dep_KCNQ3. DR InterPro; IPR013821; K_chnl_volt-dep_KCNQ_C. DR PANTHER; PTHR47735:SF11; POTASSIUM VOLTAGE-GATED CHANNEL SUBFAMILY KQT MEMBER 3; 1. DR PANTHER; PTHR47735; POTASSIUM VOLTAGE-GATED CHANNEL SUBFAMILY KQT MEMBER 4; 1. DR Pfam; PF00520; Ion_trans; 1. DR Pfam; PF03520; KCNQ_channel; 1. DR Pfam; PF11956; KCNQC3-Ank-G_bd; 1. DR PRINTS; PR00169; KCHANNEL. DR PRINTS; PR01462; KCNQ3CHANNEL. DR PRINTS; PR01459; KCNQCHANNEL. DR SUPFAM; SSF81324; Voltage-gated potassium channels; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cell membrane; Disease variant; KW Epilepsy; Ion channel; Ion transport; Membrane; Phosphoprotein; Potassium; KW Potassium channel; Potassium transport; Reference proteome; Transmembrane; KW Transmembrane helix; Transport; Ubl conjugation; Voltage-gated channel. FT CHAIN 1..872 FT /note="Potassium voltage-gated channel subfamily KQT member FT 3" FT /id="PRO_0000054034" FT TOPO_DOM 1..121 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 122..142 FT /note="Helical; Name=Segment S1" FT /evidence="ECO:0000255" FT TOPO_DOM 143..152 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 153..173 FT /note="Helical; Name=Segment S2" FT /evidence="ECO:0000255" FT TOPO_DOM 174..196 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 197..217 FT /note="Helical; Name=Segment S3" FT /evidence="ECO:0000255" FT TOPO_DOM 218..225 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 226..247 FT /note="Helical; Voltage-sensor; Name=Segment S4" FT /evidence="ECO:0000255" FT TOPO_DOM 248..261 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 262..282 FT /note="Helical; Name=Segment S5" FT /evidence="ECO:0000255" FT TOPO_DOM 283..303 FT /note="Extracellular" FT /evidence="ECO:0000255" FT INTRAMEM 304..324 FT /note="Pore-forming; Name=Segment H5" FT /evidence="ECO:0000255" FT TOPO_DOM 325..330 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 331..351 FT /note="Helical; Name=Segment S6" FT /evidence="ECO:0000255" FT TOPO_DOM 352..872 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT REGION 1..43 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 356..537 FT /note="Mediates interaction with calmodulin" FT /evidence="ECO:0000269|PubMed:27564677" FT REGION 575..611 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 764..872 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 316..321 FT /note="Selectivity filter" FT /evidence="ECO:0000250" FT COMPBIAS 579..611 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 841..872 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 81 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:O88944" FT MOD_RES 246 FT /note="Phosphothreonine" FT /evidence="ECO:0000269|PubMed:16319223" FT VAR_SEQ 1..9 FT /note="MGLKARRAA -> MKPAEHATM (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_044906" FT VAR_SEQ 10..129 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_044907" FT VARIANT 305 FT /note="D -> G (in BFNS2; reduces the maximal heteromeric FT current by 40% with no alteration in voltage dependence of FT activation or deactivation kinetics; dbSNP:rs118192248)" FT /evidence="ECO:0000269|PubMed:14534157" FT /id="VAR_026994" FT VARIANT 309 FT /note="W -> R (in BFNS2; dbSNP:rs118192249)" FT /evidence="ECO:0000269|PubMed:10852552" FT /id="VAR_010935" FT VARIANT 310 FT /note="G -> V (in BFNS2; about 50% reduction of wild-type FT heteromeric current; ratio of 1:1; or 20%; ratio of 1:1:2; FT dbSNP:rs118192250)" FT /evidence="ECO:0000269|PubMed:14534157, FT ECO:0000269|PubMed:9425900, ECO:0000269|PubMed:9872318" FT /id="VAR_001546" FT VARIANT 340 FT /note="G -> V (in BFNS2; unknown pathological FT significance)" FT /evidence="ECO:0000269|PubMed:25982755" FT /id="VAR_078681" FT VARIANT 414 FT /note="E -> G (in dbSNP:rs2303995)" FT /id="VAR_053859" FT VARIANT 468 FT /note="N -> S (has no statistically significant effect on FT the current or biophysical properties of the heteromeric FT channel; dbSNP:rs118192252)" FT /evidence="ECO:0000269|PubMed:14534157" FT /id="VAR_026995" FT VARIANT 574 FT /note="P -> S (rare variant; found in a patient with FT rolandic epilepsy and additional features such as mild FT developmental delay and abnormal behavior; unknown FT pathological significance; dbSNP:rs74582884)" FT /evidence="ECO:0000269|PubMed:22612257" FT /id="VAR_072741" FT VARIANT 780 FT /note="R -> C (found in patients with benign familial FT infantile seizures; unknown pathological significance; FT dbSNP:rs138852641)" FT /evidence="ECO:0000269|PubMed:23360469" FT /id="VAR_078682" FT MUTAGEN 246 FT /note="T->A: No effect on current or expression." FT /evidence="ECO:0000269|PubMed:16319223" FT MUTAGEN 246 FT /note="T->D: Abolishes currents without reducing channel FT protein expression." FT /evidence="ECO:0000269|PubMed:16319223" FT MUTAGEN 318 FT /note="G->S: >50% Reduction of wt heteromeric current; FT ratio of 1:1 and 1:1:2." FT /evidence="ECO:0000269|PubMed:9872318" FT CONFLICT 62 FT /note="D -> N (in Ref. 5; AAI28577)" FT /evidence="ECO:0000305" FT CONFLICT 233 FT /note="Q -> L (in Ref. 3; BAG58996)" FT /evidence="ECO:0000305" FT HELIX 373..386 FT /evidence="ECO:0007829|PDB:5J03" FT HELIX 397..403 FT /evidence="ECO:0007829|PDB:5J03" SQ SEQUENCE 872 AA; 96742 MW; BB79C69EE8591A84 CRC64; MGLKARRAAG AAGGGGDGGG GGGGAANPAG GDAAAAGDEE RKVGLAPGDV EQVTLALGAG ADKDGTLLLE GGGRDEGQRR TPQGIGLLAK TPLSRPVKRN NAKYRRIQTL IYDALERPRG WALLYHALVF LIVLGCLILA VLTTFKEYET VSGDWLLLLE TFAIFIFGAE FALRIWAAGC CCRYKGWRGR LKFARKPLCM LDIFVLIASV PVVAVGNQGN VLATSLRSLR FLQILRMLRM DRRGGTWKLL GSAICAHSKE LITAWYIGFL TLILSSFLVY LVEKDVPEVD AQGEEMKEEF ETYADALWWG LITLATIGYG DKTPKTWEGR LIAATFSLIG VSFFALPAGI LGSGLALKVQ EQHRQKHFEK RRKPAAELIQ AAWRYYATNP NRIDLVATWR FYESVVSFPF FRKEQLEAAS SQKLGLLDRV RLSNPRGSNT KGKLFTPLNV DAIEESPSKE PKPVGLNNKE RFRTAFRMKA YAFWQSSEDA GTGDPMAEDR GYGNDFPIED MIPTLKAAIR AVRILQFRLY KKKFKETLRP YDVKDVIEQY SAGHLDMLSR IKYLQTRIDM IFTPGPPSTP KHKKSQKGSA FTFPSQQSPR NEPYVARPST SEIEDQSMMG KFVKVERQVQ DMGKKLDFLV DMHMQHMERL QVQVTEYYPT KGTSSPAEAE KKEDNRYSDL KTIICNYSET GPPEPPYSFH QVTIDKVSPY GFFAHDPVNL PRGGPSSGKV QATPPSSATT YVERPTVLPI LTLLDSRVSC HSQADLQGPY SDRISPRQRR SITRDSDTPL SLMSVNHEEL ERSPSGFSIS QDRDDYVFGP NGGSSWMREK RYLAEGETDT DTDPFTPSGS MPLSSTGDGI SDSVWTPSNK PI //