ID   KCNQ3_RAT               Reviewed;         873 AA.
AC   O88944; Q9Z240;
DT   01-JUN-2001, integrated into UniProtKB/Swiss-Prot.
DT   19-DEC-2001, sequence version 2.
DT   24-JAN-2024, entry version 168.
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|RGD:69222};
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC   TISSUE=Brain;
RA   Derst C., Preisig-Mueller R., Hennighausen A., Daut J.;
RL   Submitted (SEP-2001) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, AND SUBCELLULAR LOCATION.
RC   TISSUE=Brain;
RX   PubMed=9836639; DOI=10.1126/science.282.5395.1890;
RA   Wang H.-S., Pan Z., Shi W., Brown B.S., Wymore R.S., Cohen I.S.,
RA   Dixon J.E., McKinnon D.;
RT   "KCNQ2 and KCNQ3 potassium channel subunits: molecular correlates of the M-
RT   channel.";
RL   Science 282:1890-1893(1998).
RN   [3]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-82, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=22673903; DOI=10.1038/ncomms1871;
RA   Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA   Olsen J.V.;
RT   "Quantitative maps of protein phosphorylation sites across 14 different rat
RT   organs and tissues.";
RL   Nat. Commun. 3:876-876(2012).
RN   [4]
RP   INTERACTION WITH IQCJ-SCHIP1.
RX   PubMed=27979964; DOI=10.1074/jbc.m116.758029;
RA   Martin P.M., Cifuentes-Diaz C., Devaux J., Garcia M., Bureau J.,
RA   Thomasseau S., Klingler E., Girault J.A., Goutebroze L.;
RT   "Schwannomin-interacting protein 1 isoform IQCJ-SCHIP1 is a multipartner
RT   ankyrin- and spectrin-binding protein involved in the organization of nodes
RT   of Ranvier.";
RL   J. Biol. Chem. 292:2441-2456(2017).
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 (PubMed:9836639). KCNQ2-KCNQ3 channel is
CC       selectively permeable to other cations besides potassium, in decreasing
CC       order of affinity K(+) > Rb(+) > Cs(+) > Na(+). Associates with Na(+)-
CC       coupled myo-inositol symporter SLC5A3 forming a coregulatory complex
CC       that alters ion selectivity, increasing Na(+) and Cs(+) permeation
CC       relative to K(+) permeation (By similarity).
CC       {ECO:0000250|UniProtKB:O43525, ECO:0000269|PubMed:9836639}.
CC   -!- SUBUNIT: Heterotetramer with KCNQ2; form the heterotetrameric M
CC       potassium channel. Interacts with calmodulin; the interaction is
CC       calcium-independent, constitutive and participates in the proper
CC       assembly of a functional heterotetrameric M channel. Heteromultimer
CC       with KCNQ5. May associate with KCNE2. Interacts with IQCJ-SCHIP1
CC       (PubMed:27979964). {ECO:0000250|UniProtKB:O43525,
CC       ECO:0000269|PubMed:27979964}.
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:9836639};
CC       Multi-pass membrane protein {ECO:0000255}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=O88944-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=O88944-2; Sequence=VSP_001012;
CC   -!- TISSUE SPECIFICITY: Expressed in brain and sympathetic ganglia. In
CC       brain, expressed in cortex, hippocampus and at much lower levels in
CC       cerebellum. In sympathetic ganglia, expressed at approximately equal
CC       levels in both superior cervical ganglia and prevertebral ganglia.
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. Degradation induced by NEDD4L is inhibited by
CC       USP36. {ECO:0000250|UniProtKB:O43525}.
CC   -!- SIMILARITY: Belongs to the potassium channel family. KQT (TC 1.A.1.15)
CC       subfamily. Kv7.3/KCNQ3 sub-subfamily. {ECO:0000305}.
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DR   EMBL; AF087454; AAC36723.2; -; mRNA.
DR   EMBL; AF091247; AAC79846.1; -; mRNA.
DR   RefSeq; NP_113785.3; NM_031597.4. [O88944-1]
DR   AlphaFoldDB; O88944; -.
DR   SMR; O88944; -.
DR   CORUM; O88944; -.
DR   STRING; 10116.ENSRNOP00000065354; -.
DR   BindingDB; O88944; -.
DR   ChEMBL; CHEMBL5531; -.
DR   DrugCentral; O88944; -.
DR   GuidetoPHARMACOLOGY; 562; -.
DR   iPTMnet; O88944; -.
DR   PhosphoSitePlus; O88944; -.
DR   PaxDb; 10116-ENSRNOP00000065354; -.
DR   Ensembl; ENSRNOT00000109659.1; ENSRNOP00000093985.1; ENSRNOG00000005206.8. [O88944-1]
DR   Ensembl; ENSRNOT00055043647; ENSRNOP00055035637; ENSRNOG00055025295. [O88944-1]
DR   Ensembl; ENSRNOT00060006715; ENSRNOP00060005051; ENSRNOG00060004007. [O88944-1]
DR   Ensembl; ENSRNOT00065006485; ENSRNOP00065004552; ENSRNOG00065004436. [O88944-1]
DR   GeneID; 29682; -.
DR   KEGG; rno:29682; -.
DR   UCSC; RGD:69222; rat. [O88944-1]
DR   AGR; RGD:69222; -.
DR   CTD; 3786; -.
DR   RGD; 69222; Kcnq3.
DR   eggNOG; KOG1419; Eukaryota.
DR   GeneTree; ENSGT00940000159760; -.
DR   InParanoid; O88944; -.
DR   OMA; QDRDDYM; -.
DR   PhylomeDB; O88944; -.
DR   PRO; PR:O88944; -.
DR   Proteomes; UP000002494; Chromosome 7.
DR   GO; GO:0043194; C:axon initial segment; IDA:RGD.
DR   GO; GO:0009986; C:cell surface; IDA:RGD.
DR   GO; GO:0030425; C:dendrite; IDA:RGD.
DR   GO; GO:0005739; C:mitochondrion; IEA:GOC.
DR   GO; GO:0043025; C:neuronal cell body; IDA:RGD.
DR   GO; GO:0033268; C:node of Ranvier; ISO:RGD.
DR   GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR   GO; GO:0036477; C:somatodendritic compartment; IDA:RGD.
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:RGD.
DR   GO; GO:0005267; F:potassium channel activity; ISO:RGD.
DR   GO; GO:0019901; F:protein kinase binding; IPI:RGD.
DR   GO; GO:0044325; F:transmembrane transporter binding; IPI:RGD.
DR   GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:RGD.
DR   GO; GO:0005244; F:voltage-gated monoatomic ion channel activity; ISO:RGD.
DR   GO; GO:0005249; F:voltage-gated potassium channel activity; IDA:UniProtKB.
DR   GO; GO:0099610; P:action potential initiation; ISO:RGD.
DR   GO; GO:0097314; P:apoptosome assembly; ISO:RGD.
DR   GO; GO:0071242; P:cellular response to ammonium ion; IMP:RGD.
DR   GO; GO:0071277; P:cellular response to calcium ion; ISO:RGD.
DR   GO; GO:0071466; P:cellular response to xenobiotic stimulus; ISO:RGD.
DR   GO; GO:0006897; P:endocytosis; ISO:RGD.
DR   GO; GO:0051649; P:establishment of localization in cell; ISO:RGD.
DR   GO; GO:0098976; P:excitatory chemical synaptic transmission; ISO:RGD.
DR   GO; GO:0006887; P:exocytosis; ISO:RGD.
DR   GO; GO:0061548; P:ganglion development; IEP:RGD.
DR   GO; GO:0010467; P:gene expression; ISO:RGD.
DR   GO; GO:0098977; P:inhibitory chemical synaptic transmission; ISO:RGD.
DR   GO; GO:0060081; P:membrane hyperpolarization; ISO:RGD.
DR   GO; GO:0051882; P:mitochondrial depolarization; ISO:RGD.
DR   GO; GO:0034220; P:monoatomic ion transmembrane transport; IMP:RGD.
DR   GO; GO:0021675; P:nerve development; ISO:RGD.
DR   GO; GO:0051402; P:neuron apoptotic process; ISO:RGD.
DR   GO; GO:0030182; P:neuron differentiation; ISO:RGD.
DR   GO; GO:0016322; P:neuron remodeling; ISO:RGD.
DR   GO; GO:0019228; P:neuronal action potential; ISO:RGD.
DR   GO; GO:0014003; P:oligodendrocyte development; IEP:RGD.
DR   GO; GO:0071805; P:potassium ion transmembrane transport; IDA:UniProtKB.
DR   GO; GO:0006606; P:protein import into nucleus; ISO:RGD.
DR   GO; GO:0006605; P:protein targeting; ISO:RGD.
DR   GO; GO:0015031; P:protein transport; ISO:RGD.
DR   GO; GO:0065003; P:protein-containing complex assembly; ISO:RGD.
DR   GO; GO:0036343; P:psychomotor behavior; ISO:RGD.
DR   GO; GO:0099611; P:regulation of action potential firing threshold; ISO:RGD.
DR   GO; GO:0048167; P:regulation of synaptic plasticity; ISO:RGD.
DR   GO; GO:0010996; P:response to auditory stimulus; ISO:RGD.
DR   GO; GO:0009612; P:response to mechanical stimulus; ISO:RGD.
DR   GO; GO:0014070; P:response to organic cyclic compound; ISO:RGD.
DR   GO; GO:0007605; P:sensory perception of sound; ISO:RGD.
DR   GO; GO:1903701; P:substantia propria of cornea development; ISO:RGD.
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.
DR   Genevisible; O88944; RN.
PE   1: Evidence at protein level;
KW   Alternative splicing; Cell membrane; Ion channel; Ion transport; Membrane;
KW   Phosphoprotein; Potassium; Potassium channel; Potassium transport;
KW   Reference proteome; Transmembrane; Transmembrane helix; Transport;
KW   Ubl conjugation; Voltage-gated channel.
FT   CHAIN           1..873
FT                   /note="Potassium voltage-gated channel subfamily KQT member
FT                   3"
FT                   /id="PRO_0000054036"
FT   TOPO_DOM        1..122
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        123..143
FT                   /note="Helical; Name=Segment S1"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        144..153
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        154..174
FT                   /note="Helical; Name=Segment S2"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        175..197
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        198..218
FT                   /note="Helical; Name=Segment S3"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        219..226
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        227..248
FT                   /note="Helical; Voltage-sensor; Name=Segment S4"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        249..262
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        263..283
FT                   /note="Helical; Name=Segment S5"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        284..304
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000305"
FT   INTRAMEM        305..325
FT                   /note="Pore-forming; Name=Segment H5"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        326..331
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        332..352
FT                   /note="Helical; Name=Segment S6"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        353..873
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   REGION          1..41
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          357..538
FT                   /note="Mediates interaction with calmodulin"
FT                   /evidence="ECO:0000250|UniProtKB:O43525"
FT   REGION          575..603
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          723..742
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          766..873
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           317..322
FT                   /note="Selectivity filter"
FT                   /evidence="ECO:0000250"
FT   COMPBIAS        580..603
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        725..742
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        842..873
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         82
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0007744|PubMed:22673903"
FT   VAR_SEQ         1..83
FT                   /note="MGLKARRAAGAAGGGGGEGGGGGGGAANPAGGDSAVAGDEERKVGLAPGDVE
FT                   QVTLALGTGADKDGTLLLEGGGREEGQRRTP -> MALEFPGLQPPPPPRPRTPSAPSS
FT                   RSSSGEGEAPSGGEADGAQGS (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:9836639"
FT                   /id="VSP_001012"
FT   CONFLICT        654
FT                   /note="H -> R (in Ref. 2; AAC79846)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   873 AA;  96898 MW;  D77AF88088051E15 CRC64;
     MGLKARRAAG AAGGGGGEGG GGGGGAANPA GGDSAVAGDE ERKVGLAPGD VEQVTLALGT
     GADKDGTLLL EGGGREEGQR RTPQGIGLLA KTPLSRPVKR NNAKYRRIQT LIYDALERPR
     GWALLYHALV FLIVLGCLIL AVLTTFKEYE TVSGDWLLLL ETFAIFIFGA EFALRIWAAG
     CCCRYKGWRG RLKFARKPLC MLDIFVLIAS VPVVAVGNQG NVLATSLRSL RFLQILRMLR
     MDRRGGTWKL LGSAICAHSK ELITAWYIGF LTLILSSFLV YLVEKDVPEM DAQGEEMKEE
     FETYADALWW GLITLATIGY GDKTPKTWEG RLIAATFSLI GVSFFALPAG ILGSGLALKV
     QEQHRQKHFE KRRKPAAELI QAAWRYYATN PNRLDLVATW RFYESVVSFP FFRKEQLEAA
     ASQKLGLLDR VRLSNPRGSN TKGKLFTPLN VDAIEESPSK EPKPVGLNNK ERFRTAFRMK
     AYAFWQSSED AGTGDPMTED RGYGNDFLIE DMIPTLKAAI RAVRILQFRL YKKKFKETLR
     PYDVKDVIEQ YSAGHLDMLS RIKYLQTRID MIFTPGPPST PKHKKSQKGS AFTYPSQQSP
     RNEPYVARAA TSETEDQSMM GKFVKVERQV HDMGKKLDFL VDMHMQHMER LQVHVTEYYP
     TKGASSPAEG EKKEDNRYSD LKTIICNYSE SGPPDPPYSF HQVPIDRVGP YGFFAHDPVK
     LTRGGPSSTK AQANLPSSGS TYAERPTVLP ILTLLDSCVS YHSQTELQGP YSDHISPRQR
     RSITRDSDTP LSLMSVNHEE LERSPSGFSI SQDRDDYVFG PSGGSSWMRE KRYLAEGETD
     TDTDPFTPSG SMPMSSTGDG ISDSIWTPSN KPT
//