KCNE4_HUMAN
ID KCNE4_HUMAN Reviewed; 221 AA.
AC Q8WWG9; B7Z275; Q53SM4; Q96CC4;
DT 28-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT 03-SEP-2014, sequence version 4.
DT 03-AUG-2022, entry version 153.
DE RecName: Full=Potassium voltage-gated channel subfamily E member 4;
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;
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 [LARGE SCALE MRNA].
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 [2]
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 23-221, AND VARIANT 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 [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 25-221, 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 [5]
RP ASSOCIATION 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 [6]
RP 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 [7]
RP 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).
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. May associate with KCNQ1/KVLTQ1 and inhibit potassium current.
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}; Single-pass membrane
CC protein {ECO:0000305}.
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 -!- 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};
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DR EMBL; AK294423; BAH11761.1; -; mRNA.
DR EMBL; AC017014; AAX93228.1; -; 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.
DR AlphaFoldDB; Q8WWG9; -.
DR SMR; Q8WWG9; -.
DR BioGRID; 117217; 42.
DR CORUM; Q8WWG9; -.
DR IntAct; Q8WWG9; 4.
DR STRING; 9606.ENSP00000281830; -.
DR DrugBank; DB00228; Enflurane.
DR DrugBank; DB01110; Miconazole.
DR DrugBank; DB01069; Promethazine.
DR GlyGen; Q8WWG9; 1 site.
DR iPTMnet; Q8WWG9; -.
DR PhosphoSitePlus; Q8WWG9; -.
DR BioMuta; KCNE4; -.
DR DMDM; 311033433; -.
DR jPOST; Q8WWG9; -.
DR PaxDb; Q8WWG9; -.
DR PeptideAtlas; Q8WWG9; -.
DR PRIDE; Q8WWG9; -.
DR ProteomicsDB; 74885; -.
DR Antibodypedia; 2515; 140 antibodies from 27 providers.
DR DNASU; 23704; -.
DR Ensembl; ENST00000281830.4; ENSP00000281830.5; ENSG00000152049.7.
DR GeneID; 23704; -.
DR KEGG; hsa:23704; -.
DR UCSC; uc002vnl.7; human.
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 PharmGKB; PA30032; -.
DR VEuPathDB; HostDB:ENSG00000152049; -.
DR eggNOG; ENOG502RZ36; Eukaryota.
DR HOGENOM; CLU_109412_0_0_1; -.
DR InParanoid; Q8WWG9; -.
DR OMA; HFTIQEE; -.
DR OrthoDB; 1418062at2759; -.
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 935 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 131 other tissues.
DR Genevisible; Q8WWG9; HS.
DR GO; GO:0016324; C:apical plasma membrane; IEA:Ensembl.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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:1902260; P:negative regulation of delayed rectifier potassium channel activity; IBA:GO_Central.
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; PTHR15282; 1.
DR Pfam; PF02060; ISK_Channel; 1.
DR PRINTS; PR00168; KCNECHANNEL.
PE 1: Evidence at protein level;
KW Glycoprotein; Ion channel; Ion transport; Membrane; Potassium;
KW Potassium channel; Potassium transport; Reference proteome; Transmembrane;
KW 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 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.4"
FT /id="VAR_024411"
FT CONFLICT 47
FT /note="V -> A (in Ref. 1; BAH11761)"
FT /evidence="ECO:0000305"
FT CONFLICT 105
FT /note="M -> V (in Ref. 4; AAL49979)"
FT /evidence="ECO:0000305"
FT CONFLICT 137
FT /note="P -> S (in Ref. 4; 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
