KCNQ2_RAT
ID KCNQ2_RAT Reviewed; 852 AA.
AC O88943;
DT 01-JUN-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 25-MAY-2022, entry version 164.
DE RecName: Full=Potassium voltage-gated channel subfamily KQT member 2 {ECO:0000305};
DE AltName: Full=KQT-like 2;
DE AltName: Full=Potassium channel subunit alpha KvLQT2;
DE AltName: Full=Voltage-gated potassium channel subunit Kv7.2;
GN Name=Kcnq2 {ECO:0000312|RGD:621504};
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 A).
RC TISSUE=Brain;
RA Derst C., Preisig-Mueller R., Hennighausen A., Daut J.;
RL Submitted (AUG-1998) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A), FUNCTION, AND SUBCELLULAR LOCATION.
RC TISSUE=Brain;
RX PubMed=11038262; DOI=10.1016/s0169-328x(00)00146-7;
RA Jow F., Wang K.-W.;
RT "Cloning and functional expression of rKCNQ2 K(+) channel from rat brain.";
RL Brain Res. Mol. Brain Res. 80:269-278(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], ALTERNATIVE SPLICING, FUNCTION, SUBCELLULAR
RP LOCATION, AND SUBUNIT.
RC TISSUE=Brain, and Sympathetic ganglion;
RX PubMed=11230508; DOI=10.1111/j.1469-7793.2001.0347i.x;
RA Pan Z., Selyanko A.A., Hadley J.K., Brown D.A., Dixon J.E., McKinnon D.;
RT "Alternative splicing of KCNQ2 potassium channel transcripts contributes to
RT the functional diversity of M-currents.";
RL J. Physiol. (Lond.) 531:347-358(2001).
RN [4]
RP TISSUE SPECIFICITY.
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 [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-489; SER-655; SER-781 AND
RP SER-783, AND IDENTIFICATION BY 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).
CC -!- FUNCTION: Associates with KCNQ3 to form a potassium channel with
CC essentially identical properties to the channel underlying the native
CC M-current, a slowly activating and deactivating potassium conductance
CC which plays a critical role in determining the subthreshold electrical
CC excitability of neurons as well as the responsiveness to synaptic
CC inputs. Therefore, it is important in the regulation of neuronal
CC excitability. KCNQ2 current is blocked by barium and tetraethylammonium
CC whereas 4-aminopyridine and charybdotoxin have no effect on KCNQ2
CC current. Tyrosine kinase inhibitors genistein or herbimycin a markedly
CC down-regulate KCNQ2 current. As the native M-channel, the potassium
CC channel composed of KCNQ2 and KCNQ3 is also suppressed by activation of
CC the muscarinic acetylcholine receptor CHRM1.
CC {ECO:0000269|PubMed:11038262, ECO:0000269|PubMed:11230508}.
CC -!- SUBUNIT: Heterotetramer with KCNQ3; form the heterotetrameric M
CC potassium channel (PubMed:11230508). Interacts with calmodulin; the
CC interaction is calcium-independent, constitutive and participates in
CC the proper assembly of a functional heterotetrameric M channel. May
CC associate with KCNE2 (By similarity). Interacts with IQCJ-SCHIP1 (By
CC similarity). {ECO:0000250|UniProtKB:O43526,
CC ECO:0000250|UniProtKB:Q9Z351, ECO:0000269|PubMed:11230508}.
CC -!- INTERACTION:
CC O88943; P62161: Calm3; NbExp=4; IntAct=EBI-7900557, EBI-397530;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:11038262,
CC ECO:0000269|PubMed:11230508}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=9;
CC Comment=Splice isoforms fell into three classes, those that contain
CC an in frame exon 16 (Isoforms A-I) those that contain an out-of-frame
CC exon 16 due to an alternative splice junction in exon 14 and those
CC that terminate prematurely to exon 16. Only the forms containing an
CC in frame exon 16 are able to form functional channels. A similar
CC splice pattern is also produced for splice variants that contain an
CC out-of-frame exon 16. A wide variety of different truncated isoforms
CC were isolated for splice variants that terminate prematurely to exon
CC 16.;
CC Name=A;
CC IsoId=O88943-1; Sequence=Displayed;
CC Name=B;
CC IsoId=O88943-2; Sequence=VSP_001009, VSP_001011;
CC Name=C;
CC IsoId=O88943-3; Sequence=VSP_001007;
CC Name=D;
CC IsoId=O88943-4; Sequence=VSP_001008, VSP_001010;
CC Name=E;
CC IsoId=O88943-5; Sequence=VSP_001008;
CC Name=F;
CC IsoId=O88943-6; Sequence=VSP_001007, VSP_001008, VSP_001010;
CC Name=G;
CC IsoId=O88943-7; Sequence=VSP_001011;
CC Name=H;
CC IsoId=O88943-8; Sequence=VSP_001007, VSP_001008;
CC Name=I;
CC IsoId=O88943-9; Sequence=VSP_001010;
CC -!- TISSUE SPECIFICITY: Expressed in brain and sympathetic ganglia. In
CC brain, expressed in cortex, hippocampus, and cerebellum. In sympathetic
CC ganglia, expressed at lower levels in celiac ganglia and superior
CC mesenteric ganglia than in superior cervical ganglia.
CC {ECO:0000269|PubMed:9836639}.
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 heteromeric current can be increased by intracellular
CC cyclic AMP, an effect that depends on phosphorylation of Ser-52 in the
CC N-terminal region. {ECO:0000250|UniProtKB:O43526}.
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:O43526}.
CC -!- MISCELLANEOUS: When coexpressed with KCNQ3 subunit in CHO cells or
CC Xenopus oocytes, isoform B was found to have significantly different
CC deactivation-activation kinetics. The kinetics was 2.5 times more
CC slowly than the kinetics of other isoforms. The presence of exon 15a in
CC isoform B accounts for the slow deactivation-activation kinetics.
CC Alternative splicing of the KCNQ2 gene may contribute to the variation
CC in M-current kinetics seen in vivo.
CC -!- SIMILARITY: Belongs to the potassium channel family. KQT (TC 1.A.1.15)
CC subfamily. Kv7.2/KCNQ2 sub-subfamily. {ECO:0000305}.
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DR EMBL; AF087453; AAC36722.1; -; mRNA.
DR RefSeq; NP_579856.1; NM_133322.1. [O88943-1]
DR AlphaFoldDB; O88943; -.
DR SMR; O88943; -.
DR BioGRID; 251003; 2.
DR IntAct; O88943; 1.
DR MINT; O88943; -.
DR STRING; 10116.ENSRNOP00000043732; -.
DR BindingDB; O88943; -.
DR ChEMBL; CHEMBL5530; -.
DR iPTMnet; O88943; -.
DR PhosphoSitePlus; O88943; -.
DR SwissPalm; O88943; -.
DR PaxDb; O88943; -.
DR PRIDE; O88943; -.
DR ABCD; O88943; 1 sequenced antibody.
DR GeneID; 170848; -.
DR KEGG; rno:170848; -.
DR UCSC; RGD:621504; rat. [O88943-1]
DR CTD; 3785; -.
DR RGD; 621504; Kcnq2.
DR eggNOG; KOG1419; Eukaryota.
DR InParanoid; O88943; -.
DR OrthoDB; 1168835at2759; -.
DR Reactome; R-RNO-1296072; Voltage gated Potassium channels.
DR PRO; PR:O88943; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0043194; C:axon initial segment; ISO:RGD.
DR GO; GO:0009986; C:cell surface; ISO:RGD.
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; ISO:RGD.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; IDA:RGD.
DR GO; GO:0008076; C:voltage-gated potassium channel complex; IDA:UniProtKB.
DR GO; GO:0030506; F:ankyrin binding; ISO:RGD.
DR GO; GO:0005516; F:calmodulin binding; ISS:UniProtKB.
DR GO; GO:0005251; F:delayed rectifier potassium channel activity; IBA:GO_Central.
DR GO; GO:0047485; F:protein N-terminus binding; IPI:RGD.
DR GO; GO:0005244; F:voltage-gated ion channel activity; ISO:RGD.
DR GO; GO:0005249; F:voltage-gated potassium channel activity; IDA:UniProtKB.
DR GO; GO:0060081; P:membrane hyperpolarization; ISO:RGD.
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 GO; GO:0019226; P:transmission of nerve impulse; ISO:RGD.
DR InterPro; IPR020969; Ankyrin-G_BS.
DR InterPro; IPR005821; Ion_trans_dom.
DR InterPro; IPR003937; K_chnl_volt-dep_KCNQ.
DR InterPro; IPR003947; K_chnl_volt-dep_KCNQ2.
DR InterPro; IPR013821; K_chnl_volt-dep_KCNQ_C.
DR InterPro; IPR028325; VG_K_chnl.
DR PANTHER; PTHR11537; PTHR11537; 1.
DR PANTHER; PTHR11537:SF6; PTHR11537:SF6; 1.
DR Pfam; PF00520; Ion_trans; 1.
DR Pfam; PF03520; KCNQ_channel; 1.
DR Pfam; PF11956; KCNQC3-Ank-G_bd; 1.
DR PRINTS; PR01461; KCNQ2CHANNEL.
DR PRINTS; PR01459; KCNQCHANNEL.
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..852
FT /note="Potassium voltage-gated channel subfamily KQT member
FT 2"
FT /id="PRO_0000054032"
FT TOPO_DOM 1..91
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 92..112
FT /note="Helical; Name=Segment S1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 113..122
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 123..143
FT /note="Helical; Name=Segment S2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 144..166
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 167..187
FT /note="Helical; Name=Segment S3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 188..197
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 198..221
FT /note="Helical; Voltage-sensor; Name=Segment S4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 222..231
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 232..252
FT /note="Helical; Name=Segment S5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 253..264
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT INTRAMEM 265..285
FT /note="Pore-forming; Name=Segment H5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 286..291
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 292..312
FT /note="Helical; Name=Segment S6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 313..852
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 317..522
FT /note="Mediates interaction with calmodulin"
FT /evidence="ECO:0000250|UniProtKB:O43526"
FT REGION 404..469
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 579..601
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 643..662
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 672..718
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 818..852
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 277..282
FT /note="Selectivity filter"
FT /evidence="ECO:0000250"
FT COMPBIAS 441..461
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 580..594
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 696..711
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 52
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000250|UniProtKB:O43526"
FT MOD_RES 448
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Z351"
FT MOD_RES 450
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Z351"
FT MOD_RES 454
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Z351"
FT MOD_RES 458
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Z351"
FT MOD_RES 460
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Z351"
FT MOD_RES 489
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 655
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 781
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 783
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT VAR_SEQ 373..382
FT /note="Missing (in isoform C, isoform F and isoform H)"
FT /evidence="ECO:0000305"
FT /id="VSP_001007"
FT VAR_SEQ 416
FT /note="S -> SKGRPCRGCLCGCRPGHSS (in isoform D, isoform E,
FT isoform F and isoform H)"
FT /evidence="ECO:0000305"
FT /id="VSP_001008"
FT VAR_SEQ 417..428
FT /note="Missing (in isoform B)"
FT /evidence="ECO:0000305"
FT /id="VSP_001009"
FT VAR_SEQ 491
FT /note="Missing (in isoform D, isoform F and isoform I)"
FT /evidence="ECO:0000305"
FT /id="VSP_001010"
FT VAR_SEQ 571
FT /note="R -> RIDMIVGPPPPSTPRHKKYPTKGPTAPSRESPQYSPR (in
FT isoform B and isoform G)"
FT /evidence="ECO:0000305"
FT /id="VSP_001011"
SQ SEQUENCE 852 AA; 93949 MW; 82A5FE462A5F259A CRC64;
MVQKSRNGGV YPGTSGEKKL KVGFVGLDPG APDSTRDGAL LIAGSEAPKR GSVLSKPRTG
GAGAGKPPKR NAFYRKLQNF LYNVLERPRG WAFIYHAYVF LLVFSCLVLS VFSTIKEYEK
SSEGALYILE IVTIVVFGVE YFVRIWAAGC CCRYRGWRGR LKFARKPFCV IDIMVLIASI
AVLAAGSQGN VFATSALRSL RFLQILRMIR MDRRGGTWKL LGSVVYAHSK ELVTAWYIGF
LCLILASFLV YLAEKGENDH FDTYADALWW GLITLTTIGY GDKYPQTWNG RLLAATFTLI
GVSFFALPAG ILGSGFALKV QEQHRQKHFE KRRNPAAGLI QSAWRFYATN LSRTDLHSTW
QYYERTVTVP MISSQTQTYG ASRLIPPLNQ LEMLRNLKSK SGLTFRKEPQ PEPSPSQKVS
LKDRVFSSPR GVAAKGKGSP QAQTVRRSPS ADQSLDDSPS KVPKSWSFGD RSRARQAFRI
KGAASRQNSE EASLPGEDIV EDNKSCNCEF VTEDLTPGLK VSIRAVCVMR FLVSKRKFKE
SLRPYDVMDV IEQYSAGHLD MLSRIKSLQS RVDQIVGRGP TITDKDRTKG PAETELPEDP
SMMGRLGKVE KQVLSMEKKL DFLVSIYTQR MGIPPAETEA YFGAKEPEPA PPYHSPEDSR
DHADKHGCII KIVRSTSSTG QRKYAAPPVM PPAECPPSTS WQQSHQRHGT SPVGDHGSLV
RIPPPPAHER SLSAYSGGNR ASTEFLRLEG TPACRPSEAA LRDSDTSISI PSVDHEELER
SFSGFSISQS KENLNALASC YAAVAPCAKV RPYIAEGESD TDSDLCTPCG PPPRSATGEG
PFGDVAWAGP RK
