ID KCNE4_HUMAN Reviewed; 221 AA. AC Q8WWG9; A5H1P5; B7Z275; Q53SM4; Q96CC4; DT 28-NOV-2002, integrated into UniProtKB/Swiss-Prot. DT 03-SEP-2014, sequence version 4. DT 27-MAR-2024, entry version 162. DE RecName: Full=Potassium voltage-gated channel subfamily E member 4 {ECO:0000305}; DE AltName: Full=MinK-related peptide 3; DE AltName: Full=Minimum potassium ion channel-related peptide 3; DE AltName: Full=Potassium channel subunit beta MiRP3; GN Name=KCNE4 {ECO:0000312|HGNC:HGNC:6244}; 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 [MRNA] (ISOFORM 1). RA Stockwell T.B., Busam D.A., Ferriera S.M., Brownley A.N., Strausberg R.L., RA Kirkness E.F., Rogers Y.-H., Levy S.; RL Submitted (JUN-2006) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Amygdala; 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 [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., RA Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 and RT 4."; RL Nature 434:724-731(2005). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 23-221 (ISOFORM 1), AND VARIANT RP GLU-196. RC TISSUE=Lung; 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 25-221 (ISOFORM 1), AND VARIANT GLU-196. RC TISSUE=Heart, and Kidney; RA Hui R., Teng S., Lin C., Ma L., Zhen Y.; RL Submitted (DEC-2001) to the EMBL/GenBank/DDBJ databases. RN [7] RP FUNCTION, INTERACTION WITH KCNQ1, AND TISSUE SPECIFICITY. RX PubMed=12096056; DOI=10.1113/jphysiol.2002.017301; RA Grunnet M., Jespersen T., Rasmussen H.B., Ljungstroem T., Jorgensen N.K., RA Olesen S.-P., Klaerke D.A.; RT "KCNE4 is an inhibitory subunit to the KCNQ1 channel."; RL J. Physiol. (Lond.) 542:119-130(2002). RN [8] RP FUNCTION, AND INTERACTION WITH KCNQ1. RX PubMed=19687231; DOI=10.1085/jgp.200910234; RA Vanoye C.G., Welch R.C., Daniels M.A., Manderfield L.J., Tapper A.R., RA Sanders C.R., George A.L. Jr.; RT "Distinct subdomains of the KCNQ1 S6 segment determine channel modulation RT by different KCNE subunits."; RL J. Gen. Physiol. 134:207-217(2009). RN [9] RP FUNCTION, AND INTERACTION WITH KCNQ1. RX PubMed=20533308; DOI=10.1002/jcp.22265; RA Roura-Ferrer M., Sole L., Oliveras A., Dahan R., Bielanska J., RA Villarroel A., Comes N., Felipe A.; RT "Impact of KCNE subunits on KCNQ1 (Kv7.1) channel membrane surface RT targeting."; RL J. Cell. Physiol. 225:692-700(2010). RN [10] RP FUNCTION (ISOFORMS 1 AND 2), TISSUE SPECIFICITY (ISOFORM 1), ALTERNATIVE RP SPLICING (ISOFORMS 1 AND 2), AND SUBCELLULAR LOCATION. RX PubMed=27162025; DOI=10.1096/fj.201600467r; RA Abbott G.W.; RT "Novel exon 1 protein-coding regions N-terminally extend human KCNE3 and RT KCNE4."; RL FASEB J. 30:2959-2969(2016). CC -!- FUNCTION: Ancillary protein that assembles as a beta subunit with a CC voltage-gated potassium channel complex of pore-forming alpha subunits. CC Modulates the gating kinetics and enhances stability of the channel CC complex. Associates with KCNQ1/KVLTQ1 and inhibits potassium currents. CC {ECO:0000269|PubMed:12096056, ECO:0000269|PubMed:19687231, CC ECO:0000269|PubMed:20533308, ECO:0000269|PubMed:27162025}. CC -!- FUNCTION: [Isoform 2]: May inhibit KCNQ4-mediated potassium currents. CC {ECO:0000269|PubMed:27162025}. CC -!- SUBUNIT: Interacts with KCNQ1; impairs KCNQ1 localization in lipid CC rafts and inhibits voltage-gated potassium channel activity. CC {ECO:0000269|PubMed:12096056, ECO:0000269|PubMed:19687231, CC ECO:0000269|PubMed:20533308}. CC -!- INTERACTION: CC Q8WWG9; P49069: CAMLG; NbExp=3; IntAct=EBI-11750916, EBI-1748958; CC Q8WWG9; O43681: GET3; NbExp=3; IntAct=EBI-11750916, EBI-2515857; CC Q8WWG9; Q13061-2: TRDN; NbExp=3; IntAct=EBI-11750916, EBI-17257686; CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305|PubMed:27162025}; Single- CC pass membrane protein {ECO:0000255}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative initiation; Named isoforms=2; CC Name=1; Synonyms=hKCNE4L {ECO:0000303|PubMed:27162025}; CC IsoId=Q8WWG9-1; Sequence=Displayed; CC Name=2; Synonyms=hKCNE4S {ECO:0000303|PubMed:27162025}; CC IsoId=Q8WWG9-3; Sequence=VSP_062167; CC -!- TISSUE SPECIFICITY: Predominantly expressed in embryo and adult uterus. CC Low expression found in kidney, small intestine, lung and heart. CC {ECO:0000269|PubMed:12096056}. CC -!- TISSUE SPECIFICITY: [Isoform 1]: Detected in kidney, thymus, and uterus CC (at protein level). {ECO:0000269|PubMed:27162025}. CC -!- SIMILARITY: Belongs to the potassium channel KCNE family. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAH14429.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=AAL49979.1; Type=Erroneous initiation; Note=Truncated N-terminus.; 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; DQ784806; ABQ01241.1; -; Genomic_DNA. DR EMBL; AK294423; BAH11761.1; -; mRNA. DR EMBL; AK313203; BAG36019.1; -; mRNA. DR EMBL; AC017014; AAX93228.1; -; Genomic_DNA. DR EMBL; CH471063; EAW70810.1; -; Genomic_DNA. DR EMBL; BC014429; AAH14429.1; ALT_INIT; mRNA. DR EMBL; AY065987; AAL49979.1; ALT_INIT; mRNA. DR RefSeq; NP_542402.3; NM_080671.3. [Q8WWG9-3] DR AlphaFoldDB; Q8WWG9; -. DR SMR; Q8WWG9; -. DR BioGRID; 117217; 43. DR CORUM; Q8WWG9; -. DR IntAct; Q8WWG9; 4. DR STRING; 9606.ENSP00000281830; -. DR DrugBank; DB00228; Enflurane. DR DrugBank; DB01110; Miconazole. DR DrugBank; DB01069; Promethazine. DR GlyCosmos; Q8WWG9; 1 site, No reported glycans. DR GlyGen; Q8WWG9; 1 site. DR iPTMnet; Q8WWG9; -. DR PhosphoSitePlus; Q8WWG9; -. DR BioMuta; KCNE4; -. DR DMDM; 311033433; -. DR jPOST; Q8WWG9; -. DR MassIVE; Q8WWG9; -. DR PaxDb; 9606-ENSP00000281830; -. DR PeptideAtlas; Q8WWG9; -. DR ProteomicsDB; 74885; -. DR Antibodypedia; 2515; 160 antibodies from 27 providers. DR DNASU; 23704; -. DR Ensembl; ENST00000281830.4; ENSP00000281830.5; ENSG00000152049.7. [Q8WWG9-3] DR GeneID; 23704; -. DR KEGG; hsa:23704; -. DR MANE-Select; ENST00000281830.4; ENSP00000281830.5; NM_080671.4; NP_542402.4. [Q8WWG9-3] DR UCSC; uc002vnl.7; human. [Q8WWG9-1] DR AGR; HGNC:6244; -. DR CTD; 23704; -. DR DisGeNET; 23704; -. DR GeneCards; KCNE4; -. DR HGNC; HGNC:6244; KCNE4. DR HPA; ENSG00000152049; Tissue enhanced (smooth). DR MIM; 607775; gene. DR neXtProt; NX_Q8WWG9; -. DR OpenTargets; ENSG00000152049; -. DR PharmGKB; PA30032; -. DR VEuPathDB; HostDB:ENSG00000152049; -. DR eggNOG; ENOG502RZ36; Eukaryota. DR GeneTree; ENSGT00390000013776; -. DR HOGENOM; CLU_109412_0_0_1; -. DR InParanoid; Q8WWG9; -. DR OMA; SPDVHFT; -. DR OrthoDB; 5355043at2759; -. DR TreeFam; TF333025; -. DR PathwayCommons; Q8WWG9; -. DR Reactome; R-HSA-5576890; Phase 3 - rapid repolarisation. DR Reactome; R-HSA-5576893; Phase 2 - plateau phase. DR SignaLink; Q8WWG9; -. DR BioGRID-ORCS; 23704; 7 hits in 1003 CRISPR screens. DR GeneWiki; KCNE4; -. DR GenomeRNAi; 23704; -. DR Pharos; Q8WWG9; Tbio. DR PRO; PR:Q8WWG9; -. DR Proteomes; UP000005640; Chromosome 2. DR RNAct; Q8WWG9; Protein. DR Bgee; ENSG00000152049; Expressed in saphenous vein and 132 other cell types or tissues. DR GO; GO:0016324; C:apical plasma membrane; IEA:Ensembl. DR GO; GO:0034702; C:monoatomic ion channel complex; IEA:UniProtKB-KW. DR GO; GO:0019870; F:potassium channel inhibitor activity; IDA:UniProtKB. DR GO; GO:0015459; F:potassium channel regulator activity; IBA:GO_Central. DR GO; GO:0044325; F:transmembrane transporter binding; IPI:UniProtKB. DR GO; GO:0005249; F:voltage-gated potassium channel activity; IEA:InterPro. DR GO; GO:0086011; P:membrane repolarization during action potential; IBA:GO_Central. DR GO; GO:0098915; P:membrane repolarization during ventricular cardiac muscle cell action potential; IEA:GOC. DR GO; GO:0097623; P:potassium ion export across plasma membrane; IBA:GO_Central. DR GO; GO:0086091; P:regulation of heart rate by cardiac conduction; IBA:GO_Central. DR GO; GO:0060307; P:regulation of ventricular cardiac muscle cell membrane repolarization; IBA:GO_Central. DR GO; GO:0086005; P:ventricular cardiac muscle cell action potential; IBA:GO_Central. DR InterPro; IPR000369; K_chnl_KCNE. DR PANTHER; PTHR15282; POTASSIUM VOLTAGE-GATED CHANNEL SUBFAMILY E MEMBER 1, 3; 1. DR PANTHER; PTHR15282:SF9; POTASSIUM VOLTAGE-GATED CHANNEL SUBFAMILY E MEMBER 4; 1. DR Pfam; PF02060; ISK_Channel; 1. DR PRINTS; PR00168; KCNECHANNEL. DR Genevisible; Q8WWG9; HS. PE 1: Evidence at protein level; KW Alternative initiation; Glycoprotein; Ion channel; Ion transport; Membrane; KW Potassium; Potassium channel; Potassium transport; Reference proteome; KW Transmembrane; Transmembrane helix; Transport; Voltage-gated channel. FT CHAIN 1..221 FT /note="Potassium voltage-gated channel subfamily E member FT 4" FT /id="PRO_0000144292" FT TOPO_DOM 1..86 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 87..107 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 108..221 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT REGION 58..77 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 175..221 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 61..76 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 205..221 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT CARBOHYD 9 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT VAR_SEQ 1..51 FT /note="Missing (in isoform 2)" FT /id="VSP_062167" FT VARIANT 98 FT /note="G -> S (in dbSNP:rs13409084)" FT /id="VAR_030620" FT VARIANT 196 FT /note="D -> E (in dbSNP:rs12621643)" FT /evidence="ECO:0000269|PubMed:15489334, ECO:0000269|Ref.6" FT /id="VAR_024411" FT CONFLICT 47 FT /note="V -> A (in Ref. 2; BAH11761)" FT /evidence="ECO:0000305" FT CONFLICT 105 FT /note="M -> V (in Ref. 6; AAL49979)" FT /evidence="ECO:0000305" FT CONFLICT 137 FT /note="P -> S (in Ref. 6; AAL49979)" FT /evidence="ECO:0000305" SQ SEQUENCE 221 AA; 23806 MW; F601434C18E82CFE CRC64; MHFLTIYPNC SSGVVRAQSR TEQKNPLGLD DLGIQNLGQT VSLAPAVEAA SMLKMEPLNS THPGTAASSS PLESRAAGGG SGNGNEYFYI LVVMSFYGIF LIGIMLGYMK SKRREKKSSL LLLYKDEERL WGEAMKPLPV VSGLRSVQVP LMLNMLQESV APALSCTLCS MEGDSVSSES SSPDVHLTIQ EEGADDELEE TSETPLNESS EGSSENIHQN S //