KCNE5_HUMAN
ID KCNE5_HUMAN Reviewed; 142 AA.
AC Q9UJ90; Q5JWV7;
DT 13-DEC-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 149.
DE RecName: Full=Potassium voltage-gated channel subfamily E regulatory beta subunit 5;
DE AltName: Full=AMME syndrome candidate gene 2 protein;
DE AltName: Full=Potassium channel subunit beta MiRP4;
DE AltName: Full=Potassium voltage-gated channel subfamily E member 1-like protein {ECO:0000303|PubMed:10493825};
GN Name=KCNE5; Synonyms=AMMECR2, KCNE1L {ECO:0000303|PubMed:10493825};
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], AND TISSUE SPECIFICITY.
RC TISSUE=Neuron, and Placenta;
RX PubMed=10493825; DOI=10.1006/geno.1999.5904;
RA Piccini M., Vitelli F., Seri M., Galietta L.J.V., Moran O., Bulfone A.,
RA Banfi S., Pober B., Renieri A.;
RT "KCNE1-like gene is deleted in AMME contiguous gene syndrome:
RT Identification and characterization of the human and mouse homologs.";
RL Genomics 60:251-257(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG NHLBI resequencing and genotyping service (RS&G);
RL Submitted (JUN-2006) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Heart;
RA Thomas D., Sullivan A.N., Goldstein S.A.;
RL Submitted (APR-2007) to the EMBL/GenBank/DDBJ databases.
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 INTERACTION WITH KCNQ1, AND FUNCTION.
RX PubMed=12324418; DOI=10.1016/s0006-3495(02)73961-1;
RA Angelo K., Jespersen T., Grunnet M., Nielsen M.S., Klaerke D.A.,
RA Olesen S.P.;
RT "KCNE5 induces time- and voltage-dependent modulation of the KCNQ1
RT current.";
RL Biophys. J. 83:1997-2006(2002).
RN [7]
RP SUBCELLULAR LOCATION, 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 [8]
RP POSSIBLE INVOLVEMENT IN ATS-MR.
RX PubMed=12011158; DOI=10.1136/jmg.39.5.359;
RA Meloni I., Vitelli F., Pucci L., Lowry R.B., Tonlorenzi R., Rossi E.,
RA Ventura M., Rizzoni G., Kashtan C.E., Pober B., Renieri A.;
RT "Alport syndrome and mental retardation: clinical and genetic dissection of
RT the contiguous gene deletion syndrome in Xq22.3 (ATS-MR).";
RL J. Med. Genet. 39:359-365(2002).
RN [9]
RP VARIANT SER-33.
RX PubMed=16054468; DOI=10.1016/j.amjcard.2005.03.086;
RA Ravn L.S., Hofman-Bang J., Dixen U., Larsen S.O., Jensen G., Haunso S.,
RA Svendsen J.H., Christiansen M.;
RT "Relation of 97T polymorphism in KCNE5 to risk of atrial fibrillation.";
RL Am. J. Cardiol. 96:405-407(2005).
RN [10]
RP VARIANT PHE-65, AND CHARACTERIZATION OF VARIANT PHE-65.
RX PubMed=18313602; DOI=10.1016/j.hrthm.2007.12.019;
RA Ravn L.S., Aizawa Y., Pollevick G.D., Hofman-Bang J., Cordeiro J.M.,
RA Dixen U., Jensen G., Wu Y., Burashnikov E., Haunso S., Guerchicoff A.,
RA Hu D., Svendsen J.H., Christiansen M., Antzelevitch C.;
RT "Gain of function in IKs secondary to a mutation in KCNE5 associated with
RT atrial fibrillation.";
RL Heart Rhythm 5:427-435(2008).
RN [11]
RP VARIANT HIS-81, AND CHARACTERIZATION OF VARIANT HIS-81.
RX PubMed=21493962; DOI=10.1161/circep.110.959619;
RA Ohno S., Zankov D.P., Ding W.G., Itoh H., Makiyama T., Doi T., Shizuta S.,
RA Hattori T., Miyamoto A., Naiki N., Hancox J.C., Matsuura H., Horie M.;
RT "KCNE5 (KCNE1L) variants are novel modulators of Brugada syndrome and
RT idiopathic ventricular fibrillation.";
RL Circ. Arrhythm. Electrophysiol. 4:352-361(2011).
CC -!- FUNCTION: Potassium channel ancillary subunit that is essential for
CC generation of some native K(+) currents by virtue of formation of
CC heteromeric ion channel complex with voltage-gated potassium (Kv)
CC channel pore-forming alpha subunits. Functions as an inhibitory beta-
CC subunit of the repolarizing cardiac potassium ion channel KCNQ1.
CC {ECO:0000269|PubMed:12324418}.
CC -!- SUBUNIT: Interacts with KCNQ1; impairs KCNQ1 localization in lipid
CC rafts and only conducts current upon strong and continued
CC depolarization. {ECO:0000269|PubMed:12324418,
CC ECO:0000269|PubMed:20533308}.
CC -!- INTERACTION:
CC Q9UJ90; O43681: GET3; NbExp=3; IntAct=EBI-11981259, EBI-2515857;
CC Q9UJ90; O00264: PGRMC1; NbExp=3; IntAct=EBI-11981259, EBI-1045534;
CC Q9UJ90; O43765: SGTA; NbExp=3; IntAct=EBI-11981259, EBI-347996;
CC Q9UJ90; Q96EQ0: SGTB; NbExp=3; IntAct=EBI-11981259, EBI-744081;
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000269|PubMed:20533308}; Single-
CC pass type I membrane protein {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Highly expressed in heart, skeletal muscle, brain,
CC spinal cord and placenta. {ECO:0000269|PubMed:10493825}.
CC -!- DISEASE: AMME complex (ATS-MR) [MIM:300194]: An X-linked contiguous
CC gene deletion syndrome characterized by glomerulonephritis,
CC sensorineural hearing loss, intellectual disability, midface hypoplasia
CC and elliptocytosis. {ECO:0000269|PubMed:12011158}. Note=The gene
CC represented in this entry may be involved in disease pathogenesis.
CC -!- SIMILARITY: Belongs to the potassium channel KCNE family.
CC {ECO:0000305}.
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DR EMBL; AJ012743; CAB58359.1; -; mRNA.
DR EMBL; AK314923; BAG37431.1; -; mRNA.
DR EMBL; DQ784807; ABQ01242.1; -; Genomic_DNA.
DR EMBL; EF535525; ABQ08564.1; -; mRNA.
DR EMBL; CH471120; EAX02676.1; -; Genomic_DNA.
DR EMBL; BC035330; AAH35330.1; -; mRNA.
DR CCDS; CCDS14547.1; -.
DR RefSeq; NP_036414.1; NM_012282.3.
DR AlphaFoldDB; Q9UJ90; -.
DR SMR; Q9UJ90; -.
DR BioGRID; 117161; 7.
DR CORUM; Q9UJ90; -.
DR IntAct; Q9UJ90; 4.
DR STRING; 9606.ENSP00000361173; -.
DR DrugBank; DB00228; Enflurane.
DR DrugBank; DB01110; Miconazole.
DR DrugBank; DB01069; Promethazine.
DR TCDB; 8.A.10.3.2; the slow voltage-gated k+) channel accessory protein (mink) family.
DR GlyGen; Q9UJ90; 2 sites.
DR PhosphoSitePlus; Q9UJ90; -.
DR BioMuta; KCNE5; -.
DR PaxDb; Q9UJ90; -.
DR PeptideAtlas; Q9UJ90; -.
DR PRIDE; Q9UJ90; -.
DR ProteomicsDB; 84602; -.
DR ABCD; Q9UJ90; 1 sequenced antibody.
DR Antibodypedia; 51261; 120 antibodies from 24 providers.
DR DNASU; 23630; -.
DR Ensembl; ENST00000372101.3; ENSP00000361173.2; ENSG00000176076.7.
DR GeneID; 23630; -.
DR KEGG; hsa:23630; -.
DR MANE-Select; ENST00000372101.3; ENSP00000361173.2; NM_012282.4; NP_036414.1.
DR UCSC; uc004eoh.4; human.
DR CTD; 23630; -.
DR DisGeNET; 23630; -.
DR GeneCards; KCNE5; -.
DR GeneReviews; KCNE5; -.
DR HGNC; HGNC:6241; KCNE5.
DR HPA; ENSG00000176076; Tissue enhanced (brain, skeletal muscle, tongue).
DR MalaCards; KCNE5; -.
DR MIM; 300194; phenotype.
DR MIM; 300328; gene.
DR neXtProt; NX_Q9UJ90; -.
DR OpenTargets; ENSG00000176076; -.
DR Orphanet; 86818; Alport syndrome-intellectual disability-midface hypoplasia-elliptocytosis syndrome.
DR Orphanet; 130; Brugada syndrome.
DR PharmGKB; PA30031; -.
DR VEuPathDB; HostDB:ENSG00000176076; -.
DR eggNOG; ENOG502SAHN; Eukaryota.
DR GeneTree; ENSGT00940000155001; -.
DR HOGENOM; CLU_1786304_0_0_1; -.
DR InParanoid; Q9UJ90; -.
DR OMA; EPSQACA; -.
DR OrthoDB; 1612727at2759; -.
DR PhylomeDB; Q9UJ90; -.
DR TreeFam; TF335981; -.
DR PathwayCommons; Q9UJ90; -.
DR Reactome; R-HSA-5576890; Phase 3 - rapid repolarisation.
DR Reactome; R-HSA-5576893; Phase 2 - plateau phase.
DR SignaLink; Q9UJ90; -.
DR BioGRID-ORCS; 23630; 11 hits in 697 CRISPR screens.
DR GeneWiki; KCNE1L; -.
DR GenomeRNAi; 23630; -.
DR Pharos; Q9UJ90; Tbio.
DR PRO; PR:Q9UJ90; -.
DR Proteomes; UP000005640; Chromosome X.
DR RNAct; Q9UJ90; protein.
DR Bgee; ENSG00000176076; Expressed in substantia nigra and 84 other tissues.
DR Genevisible; Q9UJ90; HS.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0008076; C:voltage-gated potassium channel complex; IDA:BHF-UCL.
DR GO; GO:0015459; F:potassium channel regulator activity; IDA:BHF-UCL.
DR GO; GO:0044325; F:transmembrane transporter binding; IPI:BHF-UCL.
DR GO; GO:0005249; F:voltage-gated potassium channel activity; IEA:InterPro.
DR GO; GO:0086014; P:atrial cardiac muscle cell action potential; IMP:BHF-UCL.
DR GO; GO:0060048; P:cardiac muscle contraction; IMP:BHF-UCL.
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:1903765; P:negative regulation of potassium ion export across plasma membrane; IDA:BHF-UCL.
DR GO; GO:1901380; P:negative regulation of potassium ion transmembrane transport; IDA:BHF-UCL.
DR GO; GO:1901381; P:positive regulation of potassium ion transmembrane transport; IDA:BHF-UCL.
DR GO; GO:0097623; P:potassium ion export across plasma membrane; IBA:GO_Central.
DR GO; GO:0060372; P:regulation of atrial cardiac muscle cell membrane repolarization; IMP:BHF-UCL.
DR GO; GO:2001257; P:regulation of cation channel activity; IDA:BHF-UCL.
DR GO; GO:0008016; P:regulation of heart contraction; IMP:BHF-UCL.
DR GO; GO:0086091; P:regulation of heart rate by cardiac conduction; IMP:BHF-UCL.
DR GO; GO:0060306; P:regulation of membrane repolarization; IDA:BHF-UCL.
DR GO; GO:1901379; P:regulation of potassium ion transmembrane transport; IDA:BHF-UCL.
DR GO; GO:0060307; P:regulation of ventricular cardiac muscle cell membrane repolarization; IMP:BHF-UCL.
DR GO; GO:0086005; P:ventricular cardiac muscle cell action potential; IMP:BHF-UCL.
DR InterPro; IPR000369; K_chnl_KCNE.
DR PANTHER; PTHR15282; PTHR15282; 1.
PE 1: Evidence at protein level;
KW Alport syndrome; Deafness; Elliptocytosis; Glycoprotein;
KW Hereditary hemolytic anemia; Intellectual disability; Membrane;
KW Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..142
FT /note="Potassium voltage-gated channel subfamily E
FT regulatory beta subunit 5"
FT /id="PRO_0000144294"
FT TRANSMEM 61..81
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 82..142
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 119..142
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 2
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 25
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VARIANT 33
FT /note="P -> S (in dbSNP:rs17003955)"
FT /evidence="ECO:0000269|PubMed:16054468"
FT /id="VAR_053037"
FT VARIANT 65
FT /note="L -> F (found in patients with atrial fibrillation;
FT unknown pathological significance; loss of its inhibitory
FT effects on KCNQ1; dbSNP:rs1364685385)"
FT /evidence="ECO:0000269|PubMed:18313602"
FT /id="VAR_072679"
FT VARIANT 81
FT /note="Y -> H (found in patients with ventricular
FT fibrillation; unknown pathological significance; loss of
FT its inhibitory effects on KCNQ1; dbSNP:rs199924386)"
FT /evidence="ECO:0000269|PubMed:21493962"
FT /id="VAR_072680"
FT VARIANT 114
FT /note="E -> Q (in dbSNP:rs41312935)"
FT /id="VAR_034048"
SQ SEQUENCE 142 AA; 14993 MW; ED8EC611CDE66BFE CRC64;
MNCSESQRLR TLLSRLLLEL HHRGNASGLG AGPRPSMGMG VVPDPFVGRE VTSAKGDDAY
LYILLIMIFY ACLAGGLILA YTRSRKLVEA KDEPSQACAE HEWAPGGALT ADAEAAAGSQ
AEGRRQLASE GLPALAQGAE RV
