KCNQ4_HUMAN
ID KCNQ4_HUMAN Reviewed; 695 AA.
AC P56696; O96025;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 22-SEP-2009, sequence version 2.
DT 03-AUG-2022, entry version 194.
DE RecName: Full=Potassium voltage-gated channel subfamily KQT member 4;
DE AltName: Full=KQT-like 4;
DE AltName: Full=Potassium channel subunit alpha KvLQT4;
DE AltName: Full=Voltage-gated potassium channel subunit Kv7.4;
GN Name=KCNQ4;
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 / MRNA] (ISOFORMS 1 AND 2), VARIANT DFNA2A
RP SER-285, VARIANT GLN-455, AND CHARACTERIZATION OF VARIANT DFNA2A SER-285.
RC TISSUE=Retina;
RX PubMed=10025409; DOI=10.1016/s0092-8674(00)80556-5;
RA Kubisch C., Schroeder B.C., Friedrich T., Luetjohann B., El-Amraoui A.,
RA Marlin S., Petit C., Jentsch T.J.;
RT "KCNQ4, a novel potassium channel expressed in sensory outer hair cells, is
RT mutated in dominant deafness.";
RL Cell 96:437-446(1999).
RN [2]
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 [3]
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 [4]
RP PHARMACOLOGICAL CHARACTERIZATION, AND POSSIBLE FUNCTION.
RX PubMed=11245603; DOI=10.1152/ajpcell.2001.280.4.c859;
RA Soegaard R., Ljungstroem T., Pedersen K.A., Oelesen S.-P., Jensen B.S.;
RT "KCNQ4 channels expressed in mammalian cells: functional characteristics
RT and pharmacology.";
RL Am. J. Physiol. 280:C859-C866(2001).
RN [5]
RP INTERACTION WITH HSP90AB1.
RX PubMed=23431407; DOI=10.1371/journal.pone.0057282;
RA Gao Y., Yechikov S., Vazquez A.E., Chen D., Nie L.;
RT "Distinct roles of molecular chaperones HSP90alpha and HSP90beta in the
RT biogenesis of KCNQ4 channels.";
RL PLoS ONE 8:E57282-E57282(2013).
RN [6]
RP MUTAGENESIS OF GLU-123; HIS-124; GLN-125; GLU-126; GLN-194; SER-205;
RP GLN-210; ARG-213; ARG-216; LYS-261; ASP-262; ASP-266; SER-268; ASP-272;
RP ASP-288; THR-290; HIS-292; LEU-295 AND VAL-298.
RX PubMed=29358396; DOI=10.1073/pnas.1714760115;
RA Luo L., Li B., Wang S., Wu F., Wang X., Liang P., Ombati R., Chen J.,
RA Lu X., Cui J., Lu Q., Zhang L., Zhou M., Tian C., Yang S., Lai R.;
RT "Centipedes subdue giant prey by blocking KCNQ channels.";
RL Proc. Natl. Acad. Sci. U.S.A. 115:1646-1651(2018).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (2.07 ANGSTROMS) OF 610-640, SUBUNIT, AND DOMAIN
RP COILED-COIL.
RX PubMed=17329207; DOI=10.1016/j.neuron.2007.02.010;
RA Howard R.J., Clark K.A., Holton J.M., Minor D.L. Jr.;
RT "Structural insight into KCNQ (Kv7) channel assembly and channelopathy.";
RL Neuron 53:663-675(2007).
RN [8]
RP VARIANTS DFNA2A SER-276; CYS-285 AND SER-321.
RX PubMed=10369879; DOI=10.1093/hmg/8.7.1321;
RA Coucke P.J., Van Hauwe P., Kelley P.M., Kunst H., Schatteman I.,
RA Van Velzen D., Meyers J., Ensink R.J., Verstreken M., Declau F., Marres H.,
RA Kastury K., Bhasin S., McGuirt W.T., Smith R.J.H., Cremers C.W.R.J.,
RA Van de Heyning P., Willems P.J., Smith S.D., Van Camp G.;
RT "Mutations in the KCNQ4 gene are responsible for autosomal dominant
RT deafness in four DFNA2 families.";
RL Hum. Mol. Genet. 8:1321-1328(1999).
RN [9]
RP VARIANT DFNA2A SER-281.
RX PubMed=10571947;
RX DOI=10.1002/(sici)1098-1004(199912)14:6<493::aid-humu8>3.0.co;2-p;
RA Talebizadeh Z., Kelley P.M., Askew J.W., Beisel K.W., Smith S.D.;
RT "Novel mutation in the KCNQ4 gene in a large kindred with dominant
RT progressive hearing loss.";
RL Hum. Mutat. 14:493-501(1999).
RN [10]
RP VARIANT DFNA2A HIS-274.
RX PubMed=10925378;
RX DOI=10.1002/1096-8628(20000731)93:3<184::aid-ajmg4>3.0.co;2-5;
RA Van Hauwe P., Coucke P.J., Ensink R.J., Huygen P., Cremers C.W.R.J.,
RA Van Camp G.;
RT "Mutations in the KCNQ4 K+ channel gene, responsible for autosomal dominant
RT hearing loss, cluster in the channel pore region.";
RL Am. J. Med. Genet. 93:184-187(2000).
RN [11]
RP VARIANT DFNA2A ARG-287.
RX PubMed=21242547; DOI=10.1001/archoto.2010.234;
RA Arnett J., Emery S.B., Kim T.B., Boerst A.K., Lee K., Leal S.M.,
RA Lesperance M.M.;
RT "Autosomal dominant progressive sensorineural hearing loss due to a novel
RT mutation in the KCNQ4 gene.";
RL Arch. Otolaryngol. Head Neck Surg. 137:54-59(2011).
CC -!- FUNCTION: Probably important in the regulation of neuronal
CC excitability. May underlie a potassium current involved in regulating
CC the excitability of sensory cells of the cochlea. KCNQ4 channels are
CC blocked by linopirdin, XE991 and bepridil, whereas clofilium is without
CC significant effect. Muscarinic agonist oxotremorine-M strongly suppress
CC KCNQ4 current in CHO cells in which cloned KCNQ4 channels were
CC coexpressed with M1 muscarinic receptors.
CC -!- SUBUNIT: Homotetramer. May form heteromultimers with KCNQ3. Interacts
CC with HSP90AB1; promotes cell surface expression of KCNQ4
CC (PubMed:23431407). {ECO:0000269|PubMed:17329207,
CC ECO:0000269|PubMed:23431407}.
CC -!- SUBCELLULAR LOCATION: Basal cell membrane; Multi-pass membrane protein.
CC Note=Situated at the basal membrane of cochlear outer hair cells.
CC {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Comment=Additional isoforms seem to exist.;
CC Name=1;
CC IsoId=P56696-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P56696-2; Sequence=VSP_001013;
CC -!- TISSUE SPECIFICITY: Expressed in the outer, but not the inner, sensory
CC hair cells of the cochlea. Slightly expressed in heart, brain and
CC skeletal muscle.
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 -!- DOMAIN: The A-domain tail carries the major determinants of channel
CC assembly specificity. Its coiled-coil region is Four-stranded.
CC {ECO:0000269|PubMed:17329207}.
CC -!- DISEASE: Deafness, autosomal dominant, 2A (DFNA2A) [MIM:600101]: A form
CC of non-syndromic sensorineural hearing loss. Sensorineural deafness
CC results from damage to the neural receptors of the inner ear, the nerve
CC pathways to the brain, or the area of the brain that receives sound
CC information. {ECO:0000269|PubMed:10025409, ECO:0000269|PubMed:10369879,
CC ECO:0000269|PubMed:10571947, ECO:0000269|PubMed:10925378,
CC ECO:0000269|PubMed:21242547}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: Mutagenesis experiments were carried out by expressing
CC in Xenopus oocytes KCNQ4 mutants either individually (homomultimers) or
CC in combination with wild-type KCNQ4 (mut/wt homomultimers) in a ratio
CC of 1:1, to mimic the situation in a heterozygous DFNA2 patient.
CC -!- SIMILARITY: Belongs to the potassium channel family. KQT (TC 1.A.1.15)
CC subfamily. Kv7.4/KCNQ4 sub-subfamily. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Hereditary hearing loss homepage; Note=Gene page;
CC URL="https://hereditaryhearingloss.org/dominant-genes";
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DR EMBL; AF105202; AAD14680.1; -; mRNA.
DR EMBL; AF105216; AAD14681.1; -; Genomic_DNA.
DR EMBL; AF105203; AAD14681.1; JOINED; Genomic_DNA.
DR EMBL; AF105204; AAD14681.1; JOINED; Genomic_DNA.
DR EMBL; AF105205; AAD14681.1; JOINED; Genomic_DNA.
DR EMBL; AF105206; AAD14681.1; JOINED; Genomic_DNA.
DR EMBL; AF105207; AAD14681.1; JOINED; Genomic_DNA.
DR EMBL; AF105208; AAD14681.1; JOINED; Genomic_DNA.
DR EMBL; AF105209; AAD14681.1; JOINED; Genomic_DNA.
DR EMBL; AF105210; AAD14681.1; JOINED; Genomic_DNA.
DR EMBL; AF105211; AAD14681.1; JOINED; Genomic_DNA.
DR EMBL; AF105212; AAD14681.1; JOINED; Genomic_DNA.
DR EMBL; AF105213; AAD14681.1; JOINED; Genomic_DNA.
DR EMBL; AF105214; AAD14681.1; JOINED; Genomic_DNA.
DR EMBL; AF105215; AAD14681.1; JOINED; Genomic_DNA.
DR EMBL; AC119677; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS456.1; -. [P56696-1]
DR RefSeq; NP_004691.2; NM_004700.3. [P56696-1]
DR RefSeq; NP_751895.1; NM_172163.2. [P56696-2]
DR PDB; 2OVC; X-ray; 2.07 A; A=610-640.
DR PDB; 4GOW; X-ray; 2.60 A; A=522-593.
DR PDB; 6N5W; X-ray; 2.15 A; A=336-362, B=524-549.
DR PDB; 7BYL; EM; 2.50 A; A/C/E/G=1-695.
DR PDB; 7BYM; EM; 3.10 A; A/C/E/G=1-695.
DR PDB; 7BYN; EM; 3.30 A; A/C/E/G=1-695.
DR PDB; 7VNP; EM; 2.79 A; A/C/E/G=2-650.
DR PDB; 7VNQ; EM; 2.96 A; A/C/E/G=2-650.
DR PDB; 7VNR; EM; 2.80 A; A/C/E/G=2-650.
DR PDBsum; 2OVC; -.
DR PDBsum; 4GOW; -.
DR PDBsum; 6N5W; -.
DR PDBsum; 7BYL; -.
DR PDBsum; 7BYM; -.
DR PDBsum; 7BYN; -.
DR PDBsum; 7VNP; -.
DR PDBsum; 7VNQ; -.
DR PDBsum; 7VNR; -.
DR AlphaFoldDB; P56696; -.
DR SMR; P56696; -.
DR BioGRID; 114580; 12.
DR CORUM; P56696; -.
DR IntAct; P56696; 1.
DR STRING; 9606.ENSP00000262916; -.
DR BindingDB; P56696; -.
DR ChEMBL; CHEMBL3576; -.
DR DrugBank; DB00228; Enflurane.
DR DrugBank; DB04953; Ezogabine.
DR DrugBank; DB06089; ICA-105665.
DR DrugBank; DB01110; Miconazole.
DR DrugBank; DB01069; Promethazine.
DR DrugCentral; P56696; -.
DR GuidetoPHARMACOLOGY; 563; -.
DR TCDB; 1.A.1.15.4; the voltage-gated ion channel (vic) superfamily.
DR iPTMnet; P56696; -.
DR PhosphoSitePlus; P56696; -.
DR BioMuta; KCNQ4; -.
DR DMDM; 259016259; -.
DR MassIVE; P56696; -.
DR PaxDb; P56696; -.
DR PeptideAtlas; P56696; -.
DR PRIDE; P56696; -.
DR ProteomicsDB; 56934; -. [P56696-1]
DR ProteomicsDB; 56935; -. [P56696-2]
DR ABCD; P56696; 1 sequenced antibody.
DR Antibodypedia; 18036; 372 antibodies from 37 providers.
DR DNASU; 9132; -.
DR Ensembl; ENST00000347132.10; ENSP00000262916.6; ENSG00000117013.17. [P56696-1]
DR Ensembl; ENST00000509682.6; ENSP00000423756.2; ENSG00000117013.17. [P56696-2]
DR GeneID; 9132; -.
DR KEGG; hsa:9132; -.
DR MANE-Select; ENST00000347132.10; ENSP00000262916.6; NM_004700.4; NP_004691.2.
DR UCSC; uc001cgh.2; human. [P56696-1]
DR CTD; 9132; -.
DR DisGeNET; 9132; -.
DR GeneCards; KCNQ4; -.
DR GeneReviews; KCNQ4; -.
DR HGNC; HGNC:6298; KCNQ4.
DR HPA; ENSG00000117013; Tissue enhanced (brain).
DR MalaCards; KCNQ4; -.
DR MIM; 600101; phenotype.
DR MIM; 603537; gene.
DR neXtProt; NX_P56696; -.
DR OpenTargets; ENSG00000117013; -.
DR Orphanet; 90635; Autosomal dominant non-syndromic sensorineural deafness type DFNA.
DR PharmGKB; PA30076; -.
DR VEuPathDB; HostDB:ENSG00000117013; -.
DR eggNOG; KOG1419; Eukaryota.
DR GeneTree; ENSGT00940000159209; -.
DR InParanoid; P56696; -.
DR OMA; EQMGEAT; -.
DR PhylomeDB; P56696; -.
DR TreeFam; TF315186; -.
DR PathwayCommons; P56696; -.
DR Reactome; R-HSA-1296072; Voltage gated Potassium channels.
DR Reactome; R-HSA-9662360; Sensory processing of sound by inner hair cells of the cochlea.
DR Reactome; R-HSA-9662361; Sensory processing of sound by outer hair cells of the cochlea.
DR SignaLink; P56696; -.
DR SIGNOR; P56696; -.
DR BioGRID-ORCS; 9132; 26 hits in 1075 CRISPR screens.
DR ChiTaRS; KCNQ4; human.
DR EvolutionaryTrace; P56696; -.
DR GeneWiki; KCNQ4; -.
DR GenomeRNAi; 9132; -.
DR Pharos; P56696; Tclin.
DR PRO; PR:P56696; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P56696; protein.
DR Bgee; ENSG00000117013; Expressed in pigmented layer of retina and 121 other tissues.
DR ExpressionAtlas; P56696; baseline and differential.
DR Genevisible; P56696; HS.
DR GO; GO:0009925; C:basal plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0008076; C:voltage-gated potassium channel complex; IBA:GO_Central.
DR GO; GO:0005516; F:calmodulin binding; IBA:GO_Central.
DR GO; GO:0005251; F:delayed rectifier potassium channel activity; IBA:GO_Central.
DR GO; GO:0005267; F:potassium channel activity; TAS:ProtInc.
DR GO; GO:0005249; F:voltage-gated potassium channel activity; IBA:GO_Central.
DR GO; GO:0042472; P:inner ear morphogenesis; IEA:Ensembl.
DR GO; GO:0071805; P:potassium ion transmembrane transport; IBA:GO_Central.
DR GO; GO:0006813; P:potassium ion transport; TAS:ProtInc.
DR GO; GO:0034765; P:regulation of ion transmembrane transport; IEA:UniProtKB-KW.
DR GO; GO:0007605; P:sensory perception of sound; TAS:ProtInc.
DR DisProt; DP02533; -.
DR InterPro; IPR005821; Ion_trans_dom.
DR InterPro; IPR003937; K_chnl_volt-dep_KCNQ.
DR InterPro; IPR013821; K_chnl_volt-dep_KCNQ_C.
DR InterPro; IPR015573; KCQN4.
DR InterPro; IPR028325; VG_K_chnl.
DR PANTHER; PTHR11537; PTHR11537; 1.
DR PANTHER; PTHR11537:SF4; PTHR11537:SF4; 1.
DR Pfam; PF00520; Ion_trans; 1.
DR Pfam; PF03520; KCNQ_channel; 1.
DR PRINTS; PR01459; KCNQCHANNEL.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell membrane; Coiled coil; Deafness;
KW Disease variant; Hearing; Ion channel; Ion transport; Membrane;
KW Non-syndromic deafness; Potassium; Potassium channel; Potassium transport;
KW Reference proteome; Transmembrane; Transmembrane helix; Transport;
KW Voltage-gated channel.
FT CHAIN 1..695
FT /note="Potassium voltage-gated channel subfamily KQT member
FT 4"
FT /id="PRO_0000054037"
FT TOPO_DOM 1..97
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 98..118
FT /note="Helical; Name=Segment S1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 119..131
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 132..152
FT /note="Helical; Name=Segment S2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 153..172
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 173..193
FT /note="Helical; Name=Segment S3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 194..201
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 202..224
FT /note="Helical; Voltage-sensor; Name=Segment S4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 225..237
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 238..258
FT /note="Helical; Name=Segment S5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 259..270
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT INTRAMEM 271..292
FT /note="Pore-forming; Name=Segment H5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 293..296
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 297..317
FT /note="Helical; Name=Segment S6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 318..695
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 1..21
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 400..480
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 496..515
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 546..650
FT /note="A-domain (Tetramerization)"
FT REGION 587..606
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 610..645
FT MOTIF 283..288
FT /note="Selectivity filter"
FT /evidence="ECO:0000250"
FT COMPBIAS 445..480
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 588..606
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 377..430
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10025409"
FT /id="VSP_001013"
FT VARIANT 274
FT /note="L -> H (in DFNA2A; dbSNP:rs80358276)"
FT /evidence="ECO:0000269|PubMed:10925378"
FT /id="VAR_010936"
FT VARIANT 276
FT /note="W -> S (in DFNA2A; dbSNP:rs80358277)"
FT /evidence="ECO:0000269|PubMed:10369879"
FT /id="VAR_008726"
FT VARIANT 281
FT /note="L -> S (in DFNA2A; dbSNP:rs80358278)"
FT /evidence="ECO:0000269|PubMed:10571947"
FT /id="VAR_010937"
FT VARIANT 285
FT /note="G -> C (in DFNA2A; loss of potassium selectivity of
FT the pore; dbSNP:rs28937588)"
FT /evidence="ECO:0000269|PubMed:10369879"
FT /id="VAR_008727"
FT VARIANT 285
FT /note="G -> S (in DFNA2A; dominant negative effect;
FT abolishes potassium current; dbSNP:rs28937588)"
FT /evidence="ECO:0000269|PubMed:10025409"
FT /id="VAR_001547"
FT VARIANT 287
FT /note="G -> R (in DFNA2A; dbSNP:rs137853969)"
FT /evidence="ECO:0000269|PubMed:21242547"
FT /id="VAR_065779"
FT VARIANT 321
FT /note="G -> S (in DFNA2A; dbSNP:rs28939710)"
FT /evidence="ECO:0000269|PubMed:10369879"
FT /id="VAR_008728"
FT VARIANT 455
FT /note="H -> Q (in dbSNP:rs34287852)"
FT /evidence="ECO:0000269|PubMed:10025409"
FT /id="VAR_058971"
FT MUTAGEN 123
FT /note="E->G: No effect on inhibition by potassium channel
FT toxin SsTX."
FT /evidence="ECO:0000269|PubMed:29358396"
FT MUTAGEN 124
FT /note="H->G: No effect on inhibition by potassium channel
FT toxin SsTX."
FT /evidence="ECO:0000269|PubMed:29358396"
FT MUTAGEN 125
FT /note="Q->G: No effect on inhibition by potassium channel
FT toxin SsTX."
FT /evidence="ECO:0000269|PubMed:29358396"
FT MUTAGEN 126
FT /note="E->G: No effect on inhibition by potassium channel
FT toxin SsTX."
FT /evidence="ECO:0000269|PubMed:29358396"
FT MUTAGEN 194
FT /note="Q->G: No effect on inhibition by potassium channel
FT toxin SsTX."
FT /evidence="ECO:0000269|PubMed:29358396"
FT MUTAGEN 196
FT /note="N->Q: No effect on inhibition by potassium channel
FT toxin SsTX."
FT /evidence="ECO:0000269|PubMed:29358396"
FT MUTAGEN 205
FT /note="S->G: No effect on inhibition by potassium channel
FT toxin SsTX."
FT /evidence="ECO:0000269|PubMed:29358396"
FT MUTAGEN 210
FT /note="Q->G: No effect on inhibition by potassium channel
FT toxin SsTX."
FT /evidence="ECO:0000269|PubMed:29358396"
FT MUTAGEN 213
FT /note="R->G: No effect on inhibition by potassium channel
FT toxin SsTX."
FT /evidence="ECO:0000269|PubMed:29358396"
FT MUTAGEN 216
FT /note="R->G: No effect on inhibition by potassium channel
FT toxin SsTX."
FT /evidence="ECO:0000269|PubMed:29358396"
FT MUTAGEN 261
FT /note="K->G: No effect on inhibition by potassium channel
FT toxin SsTX."
FT /evidence="ECO:0000269|PubMed:29358396"
FT MUTAGEN 262
FT /note="D->G: No effect on inhibition by potassium channel
FT toxin SsTX."
FT /evidence="ECO:0000269|PubMed:29358396"
FT MUTAGEN 266
FT /note="D->G: Resistant to inhibition by potassium channel
FT toxin SsTX. Normal voltage activation."
FT /evidence="ECO:0000269|PubMed:29358396"
FT MUTAGEN 268
FT /note="S->G: No effect on inhibition by potassium channel
FT toxin SsTX."
FT /evidence="ECO:0000269|PubMed:29358396"
FT MUTAGEN 272
FT /note="D->G: No effect on inhibition by potassium channel
FT toxin SsTX."
FT /evidence="ECO:0000269|PubMed:29358396"
FT MUTAGEN 288
FT /note="D->G: Resistant to inhibition by potassium channel
FT toxin SsTX. Normal voltage activation."
FT /evidence="ECO:0000269|PubMed:29358396"
FT MUTAGEN 290
FT /note="T->V: No effect on inhibition by potassium channel
FT toxin SsTX."
FT /evidence="ECO:0000269|PubMed:29358396"
FT MUTAGEN 292
FT /note="H->G: No effect on inhibition by potassium channel
FT toxin SsTX."
FT /evidence="ECO:0000269|PubMed:29358396"
FT MUTAGEN 295
FT /note="L->V: No effect on inhibition by potassium channel
FT toxin SsTX."
FT /evidence="ECO:0000269|PubMed:29358396"
FT MUTAGEN 298
FT /note="V->T: No effect on inhibition by potassium channel
FT toxin SsTX."
FT /evidence="ECO:0000269|PubMed:29358396"
FT HELIX 75..92
FT /evidence="ECO:0007829|PDB:7BYL"
FT HELIX 96..98
FT /evidence="ECO:0007829|PDB:7BYL"
FT HELIX 99..118
FT /evidence="ECO:0007829|PDB:7BYL"
FT STRAND 120..122
FT /evidence="ECO:0007829|PDB:7BYL"
FT HELIX 125..153
FT /evidence="ECO:0007829|PDB:7BYL"
FT HELIX 154..156
FT /evidence="ECO:0007829|PDB:7BYL"
FT STRAND 157..160
FT /evidence="ECO:0007829|PDB:7BYL"
FT HELIX 162..169
FT /evidence="ECO:0007829|PDB:7BYL"
FT HELIX 173..192
FT /evidence="ECO:0007829|PDB:7BYL"
FT HELIX 200..205
FT /evidence="ECO:0007829|PDB:7BYL"
FT HELIX 206..211
FT /evidence="ECO:0007829|PDB:7BYL"
FT HELIX 212..215
FT /evidence="ECO:0007829|PDB:7BYL"
FT TURN 216..221
FT /evidence="ECO:0007829|PDB:7VNR"
FT HELIX 222..233
FT /evidence="ECO:0007829|PDB:7BYL"
FT HELIX 235..260
FT /evidence="ECO:0007829|PDB:7BYL"
FT TURN 261..263
FT /evidence="ECO:0007829|PDB:7BYL"
FT HELIX 270..281
FT /evidence="ECO:0007829|PDB:7BYL"
FT STRAND 287..289
FT /evidence="ECO:0007829|PDB:7BYL"
FT HELIX 294..335
FT /evidence="ECO:0007829|PDB:7BYL"
FT HELIX 339..353
FT /evidence="ECO:0007829|PDB:6N5W"
FT TURN 355..357
FT /evidence="ECO:0007829|PDB:7BYL"
FT HELIX 359..361
FT /evidence="ECO:0007829|PDB:7BYL"
FT TURN 364..366
FT /evidence="ECO:0007829|PDB:7BYL"
FT HELIX 527..548
FT /evidence="ECO:0007829|PDB:6N5W"
FT TURN 552..555
FT /evidence="ECO:0007829|PDB:7VNR"
FT TURN 557..559
FT /evidence="ECO:0007829|PDB:7VNP"
FT HELIX 560..586
FT /evidence="ECO:0007829|PDB:7BYL"
FT HELIX 612..637
FT /evidence="ECO:0007829|PDB:2OVC"
SQ SEQUENCE 695 AA; 77101 MW; 51390F5E00E8C157 CRC64;
MAEAPPRRLG LGPPPGDAPR AELVALTAVQ SEQGEAGGGG SPRRLGLLGS PLPPGAPLPG
PGSGSGSACG QRSSAAHKRY RRLQNWVYNV LERPRGWAFV YHVFIFLLVF SCLVLSVLST
IQEHQELANE CLLILEFVMI VVFGLEYIVR VWSAGCCCRY RGWQGRFRFA RKPFCVIDFI
VFVASVAVIA AGTQGNIFAT SALRSMRFLQ ILRMVRMDRR GGTWKLLGSV VYAHSKELIT
AWYIGFLVLI FASFLVYLAE KDANSDFSSY ADSLWWGTIT LTTIGYGDKT PHTWLGRVLA
AGFALLGISF FALPAGILGS GFALKVQEQH RQKHFEKRRM PAANLIQAAW RLYSTDMSRA
YLTATWYYYD SILPSFRELA LLFEHVQRAR NGGLRPLEVR RAPVPDGAPS RYPPVATCHR
PGSTSFCPGE SSRMGIKDRI RMGSSQRRTG PSKQHLAPPT MPTSPSSEQV GEATSPTKVQ
KSWSFNDRTR FRASLRLKPR TSAEDAPSEE VAEEKSYQCE LTVDDIMPAV KTVIRSIRIL
KFLVAKRKFK ETLRPYDVKD VIEQYSAGHL DMLGRIKSLQ TRVDQIVGRG PGDRKAREKG
DKGPSDAEVV DEISMMGRVV KVEKQVQSIE HKLDLLLGFY SRCLRSGTSA SLGAVQVPLF
DPDITSDYHS PVDHEDISVS AQTLSISRSV STNMD
