KCNQ3_HUMAN
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 03-AUG-2022, entry version 200.
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] {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 [19]
RP VARIANT BFNS2 ARG-309.
RX PubMed=10852552;
RX DOI=10.1002/1531-8249(200006)47:6<822::aid-ana19>3.0.co;2-x;
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 [20]
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 [21]
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 [22]
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 [23]
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. {ECO:0000269|PubMed:11159685,
CC ECO:0000269|PubMed:14534157, ECO:0000269|PubMed:16319223,
CC 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). {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};
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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; 13.
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 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 PRIDE; O43525; -.
DR ProteomicsDB; 17526; -.
DR ProteomicsDB; 49030; -. [O43525-1]
DR Antibodypedia; 14124; 158 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 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; 1168835at2759; -.
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; 6 hits in 1065 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:0016021; C:integral component of membrane; IBA:GO_Central.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0033268; C:node of Ranvier; ISS:BHF-UCL.
DR GO; GO:0005886; C:plasma membrane; ISS:BHF-UCL.
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:0005251; F:delayed rectifier potassium channel activity; IBA:GO_Central.
DR GO; GO:0005249; F:voltage-gated potassium channel activity; IDA:UniProtKB.
DR GO; GO:0007268; P:chemical synaptic transmission; TAS:ProtInc.
DR GO; GO:0051649; P:establishment of localization in cell; IEA:Ensembl.
DR GO; GO:0060081; P:membrane hyperpolarization; IEA:Ensembl.
DR GO; GO:0071805; P:potassium ion transmembrane transport; IDA:UniProtKB.
DR GO; GO:0034765; P:regulation of ion transmembrane transport; IEA:UniProtKB-KW.
DR 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 InterPro; IPR028325; VG_K_chnl.
DR PANTHER; PTHR11537; PTHR11537; 1.
DR PANTHER; PTHR11537:SF5; PTHR11537:SF5; 1.
DR Pfam; PF00520; Ion_trans; 1.
DR Pfam; PF03520; KCNQ_channel; 1.
DR Pfam; PF11956; KCNQC3-Ank-G_bd; 1.
DR PRINTS; PR01462; KCNQ3CHANNEL.
DR PRINTS; PR01459; KCNQCHANNEL.
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
