KCNH7_HUMAN
ID KCNH7_HUMAN Reviewed; 1196 AA.
AC Q9NS40; Q53QU4; Q53TB7; Q53TP9; Q8IV15;
DT 28-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT 05-MAY-2009, sequence version 2.
DT 03-AUG-2022, entry version 182.
DE RecName: Full=Potassium voltage-gated channel subfamily H member 7;
DE AltName: Full=Ether-a-go-go-related gene potassium channel 3;
DE Short=ERG-3;
DE Short=Eag-related protein 3;
DE Short=Ether-a-go-go-related protein 3;
DE Short=hERG-3;
DE AltName: Full=Voltage-gated potassium channel subunit Kv11.3;
GN Name=KCNH7; Synonyms=ERG3;
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).
RC TISSUE=Brain;
RA Ganetzky B., Titus S.A.;
RT "Polynucleotides encoding herg-3 potassium channel.";
RL Submitted (NOV-1997) to the EMBL/GenBank/DDBJ databases.
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] (ISOFORM 2).
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 [4]
RP TISSUE SPECIFICITY.
RX PubMed=12634931; DOI=10.1007/s00424-002-0980-0;
RA Bauer C.K., Wulfsen I., Schaefer R., Glassmeier G., Wimmers S., Flitsch J.,
RA Luedecke D.K., Schwarz J.R.;
RT "HERG K(+) currents in human prolactin-secreting adenoma cells.";
RL Pflugers Arch. 445:589-600(2003).
CC -!- FUNCTION: Pore-forming (alpha) subunit of voltage-gated potassium
CC channel. Channel properties may be modulated by cAMP and subunit
CC assembly.
CC -!- SUBUNIT: The potassium channel is probably composed of a homo- or
CC heterotetrameric complex of pore-forming alpha subunits that can
CC associate with modulating beta subunits. Heteromultimer with KCNH2/ERG1
CC and KCNH6/ERG2 (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9NS40-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9NS40-2; Sequence=VSP_037116, VSP_037117, VSP_037118;
CC -!- TISSUE SPECIFICITY: Expressed in prolactin-secreting adenomas.
CC {ECO:0000269|PubMed:12634931}.
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.
CC -!- SIMILARITY: Belongs to the potassium channel family. H (Eag) (TC
CC 1.A.1.20) subfamily. Kv11.3/KCNH7 sub-subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD01946.1; Type=Frameshift; 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; AF032897; AAD01946.1; ALT_FRAME; mRNA.
DR EMBL; AC010876; AAX93139.1; -; Genomic_DNA.
DR EMBL; AC007740; AAX93153.1; -; Genomic_DNA.
DR EMBL; AC104822; AAY24106.1; -; Genomic_DNA.
DR EMBL; BC035815; AAH35815.1; -; mRNA.
DR CCDS; CCDS2219.1; -. [Q9NS40-1]
DR CCDS; CCDS2220.1; -. [Q9NS40-2]
DR RefSeq; NP_150375.2; NM_033272.3. [Q9NS40-1]
DR RefSeq; NP_775185.1; NM_173162.2. [Q9NS40-2]
DR PDB; 6Y7Q; X-ray; 1.39 A; AAA=1-135.
DR PDBsum; 6Y7Q; -.
DR AlphaFoldDB; Q9NS40; -.
DR SMR; Q9NS40; -.
DR BioGRID; 124667; 5.
DR IntAct; Q9NS40; 2.
DR MINT; Q9NS40; -.
DR STRING; 9606.ENSP00000331727; -.
DR ChEMBL; CHEMBL2362996; -.
DR DrugBank; DB01118; Amiodarone.
DR DrugBank; DB00321; Amitriptyline.
DR DrugBank; DB00590; Doxazosin.
DR DrugBank; DB00228; Enflurane.
DR DrugBank; DB00308; Ibutilide.
DR DrugBank; DB01110; Miconazole.
DR DrugBank; DB01069; Promethazine.
DR DrugBank; DB06207; Silodosin.
DR DrugBank; DB01162; Terazosin.
DR DrugCentral; Q9NS40; -.
DR GlyGen; Q9NS40; 1 site.
DR iPTMnet; Q9NS40; -.
DR PhosphoSitePlus; Q9NS40; -.
DR BioMuta; KCNH7; -.
DR DMDM; 229462892; -.
DR EPD; Q9NS40; -.
DR jPOST; Q9NS40; -.
DR MassIVE; Q9NS40; -.
DR PaxDb; Q9NS40; -.
DR PeptideAtlas; Q9NS40; -.
DR PRIDE; Q9NS40; -.
DR ProteomicsDB; 82478; -. [Q9NS40-1]
DR ProteomicsDB; 82479; -. [Q9NS40-2]
DR ABCD; Q9NS40; 2 sequenced antibodies.
DR Antibodypedia; 19119; 176 antibodies from 25 providers.
DR DNASU; 90134; -.
DR Ensembl; ENST00000328032.8; ENSP00000333781.4; ENSG00000184611.13. [Q9NS40-2]
DR Ensembl; ENST00000332142.10; ENSP00000331727.5; ENSG00000184611.13. [Q9NS40-1]
DR GeneID; 90134; -.
DR KEGG; hsa:90134; -.
DR MANE-Select; ENST00000332142.10; ENSP00000331727.5; NM_033272.4; NP_150375.2.
DR UCSC; uc002uch.3; human. [Q9NS40-1]
DR CTD; 90134; -.
DR DisGeNET; 90134; -.
DR GeneCards; KCNH7; -.
DR HGNC; HGNC:18863; KCNH7.
DR HPA; ENSG00000184611; Group enriched (brain, retina).
DR MIM; 608169; gene.
DR neXtProt; NX_Q9NS40; -.
DR OpenTargets; ENSG00000184611; -.
DR PharmGKB; PA38723; -.
DR VEuPathDB; HostDB:ENSG00000184611; -.
DR eggNOG; KOG0498; Eukaryota.
DR GeneTree; ENSGT00940000155518; -.
DR HOGENOM; CLU_005746_2_0_1; -.
DR InParanoid; Q9NS40; -.
DR OMA; RLMRTSH; -.
DR OrthoDB; 247304at2759; -.
DR PhylomeDB; Q9NS40; -.
DR TreeFam; TF313130; -.
DR PathwayCommons; Q9NS40; -.
DR Reactome; R-HSA-1296072; Voltage gated Potassium channels.
DR SignaLink; Q9NS40; -.
DR BioGRID-ORCS; 90134; 8 hits in 1067 CRISPR screens.
DR ChiTaRS; KCNH7; human.
DR GeneWiki; KCNH7; -.
DR GenomeRNAi; 90134; -.
DR Pharos; Q9NS40; Tclin.
DR PRO; PR:Q9NS40; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q9NS40; protein.
DR Bgee; ENSG00000184611; Expressed in pancreatic ductal cell and 70 other tissues.
DR ExpressionAtlas; Q9NS40; baseline and differential.
DR Genevisible; Q9NS40; HS.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0005242; F:inward rectifier potassium channel activity; IBA:GO_Central.
DR GO; GO:0044877; F:protein-containing complex binding; IEA:Ensembl.
DR GO; GO:0005249; F:voltage-gated potassium channel activity; IBA:GO_Central.
DR GO; GO:0007623; P:circadian rhythm; IEA:Ensembl.
DR GO; GO:0086011; P:membrane repolarization during action potential; IBA:GO_Central.
DR GO; GO:0071805; P:potassium ion transmembrane transport; IBA:GO_Central.
DR GO; GO:0034765; P:regulation of ion transmembrane transport; IEA:UniProtKB-KW.
DR GO; GO:0042391; P:regulation of membrane potential; IBA:GO_Central.
DR CDD; cd00038; CAP_ED; 1.
DR CDD; cd00130; PAS; 1.
DR Gene3D; 2.60.120.10; -; 1.
DR InterPro; IPR018490; cNMP-bd-like.
DR InterPro; IPR000595; cNMP-bd_dom.
DR InterPro; IPR005821; Ion_trans_dom.
DR InterPro; IPR003938; K_chnl_volt-dep_EAG/ELK/ERG.
DR InterPro; IPR003967; K_chnl_volt-dep_ERG.
DR InterPro; IPR000014; PAS.
DR InterPro; IPR035965; PAS-like_dom_sf.
DR InterPro; IPR014710; RmlC-like_jellyroll.
DR Pfam; PF00027; cNMP_binding; 1.
DR Pfam; PF00520; Ion_trans; 1.
DR Pfam; PF13426; PAS_9; 1.
DR PRINTS; PR01463; EAGCHANLFMLY.
DR PRINTS; PR01470; ERGCHANNEL.
DR SMART; SM00100; cNMP; 1.
DR SUPFAM; SSF51206; SSF51206; 1.
DR SUPFAM; SSF55785; SSF55785; 1.
DR TIGRFAMs; TIGR00229; sensory_box; 1.
DR PROSITE; PS50042; CNMP_BINDING_3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Glycoprotein; Ion channel;
KW Ion transport; Membrane; Phosphoprotein; Potassium; Potassium channel;
KW Potassium transport; Reference proteome; Transmembrane;
KW Transmembrane helix; Transport; Voltage-gated channel.
FT CHAIN 1..1196
FT /note="Potassium voltage-gated channel subfamily H member
FT 7"
FT /id="PRO_0000054015"
FT TOPO_DOM 1..412
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 413..433
FT /note="Helical; Name=Segment S1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 434..449
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 450..470
FT /note="Helical; Name=Segment S2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 471..494
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 495..515
FT /note="Helical; Name=Segment S3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 516..521
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 522..542
FT /note="Helical; Voltage-sensor; Name=Segment S4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 543..549
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 550..570
FT /note="Helical; Name=Segment S5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 571..614
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT INTRAMEM 615..635
FT /note="Pore-forming; Name=Segment H5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 636..641
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 642..662
FT /note="Helical; Name=Segment S6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 663..1196
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 41..70
FT /note="PAS"
FT DOMAIN 92..144
FT /note="PAC"
FT REGION 194..217
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 876..915
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 627..632
FT /note="Selectivity filter"
FT /evidence="ECO:0000250"
FT COMPBIAS 885..915
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 745..862
FT /ligand="a nucleoside 3',5'-cyclic phosphate"
FT /ligand_id="ChEBI:CHEBI:58464"
FT MOD_RES 174
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9ER47"
FT MOD_RES 238
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9ER47"
FT MOD_RES 319
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O54852"
FT MOD_RES 896
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O54852"
FT MOD_RES 899
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O54852"
FT CARBOHYD 600
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 298..304
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_037116"
FT VAR_SEQ 720..739
FT /note="LKGFPECLQADICLHLNQTL -> CMSVFQNESAAGIIVIAKME (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_037117"
FT VAR_SEQ 740..1196
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_037118"
FT VARIANT 958
FT /note="G -> A (in dbSNP:rs6757850)"
FT /id="VAR_057767"
FT CONFLICT 555
FT /note="L -> S (in Ref. 1; AAD01946)"
FT /evidence="ECO:0000305"
FT CONFLICT 562
FT /note="I -> N (in Ref. 1; AAD01946)"
FT /evidence="ECO:0000305"
FT CONFLICT 767..768
FT /note="PP -> LQ (in Ref. 1; AAD01946)"
FT /evidence="ECO:0000305"
FT CONFLICT 797
FT /note="I -> M (in Ref. 1; AAD01946)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1196 AA; 135000 MW; A22D046D02C2A759 CRC64;
MPVRRGHVAP QNTFLGTIIR KFEGQNKKFI IANARVQNCA IIYCNDGFCE MTGFSRPDVM
QKPCTCDFLH GPETKRHDIA QIAQALLGSE ERKVEVTYYH KNGSTFICNT HIIPVKNQEG
VAMMFIINFE YVTDNENAAT PERVNPILPI KTVNRKFFGF KFPGLRVLTY RKQSLPQEDP
DVVVIDSSKH SDDSVAMKHF KSPTKESCSP SEADDTKALI QPSKCSPLVN ISGPLDHSSP
KRQWDRLYPD MLQSSSQLSH SRSRESLCSI RRASSVHDIE GFGVHPKNIF RDRHASEDNG
RNVKGPFNHI KSSLLGSTSD SNLNKYSTIN KIPQLTLNFS EVKTEKKNSS PPSSDKTIIA
PKVKDRTHNV TEKVTQVLSL GADVLPEYKL QTPRINKFTI LHYSPFKAVW DWLILLLVIY
TAIFTPYSAA FLLNDREEQK RRECGYSCSP LNVVDLIVDI MFIIDILINF RTTYVNQNEE
VVSDPAKIAI HYFKGWFLID MVAAIPFDLL IFGSGSDETT TLIGLLKTAR LLRLVRVARK
LDRYSEYGAA VLMLLMCIFA LIAHWLACIW YAIGNVERPY LTDKIGWLDS LGQQIGKRYN
DSDSSSGPSI KDKYVTALYF TFSSLTSVGF GNVSPNTNSE KIFSICVMLI GSLMYASIFG
NVSAIIQRLY SGTARYHMQM LRVKEFIRFH QIPNPLRQRL EEYFQHAWTY TNGIDMNMVL
KGFPECLQAD ICLHLNQTLL QNCKAFRGAS KGCLRALAMK FKTTHAPPGD TLVHCGDVLT
ALYFLSRGSI EILKDDIVVA ILGKNDIFGE MVHLYAKPGK SNADVRALTY CDLHKIQRED
LLEVLDMYPE FSDHFLTNLE LTFNLRHESA KADLLRSQSM NDSEGDNCKL RRRKLSFESE
GEKENSTNDP EDSADTIRHY QSSKRHFEEK KSRSSSFISS IDDEQKPLFS GIVDSSPGIG
KASGLDFEET VPTSGRMHID KRSHSCKDIT DMRSWERENA HPQPEDSSPS ALQRAAWGIS
ETESDLTYGE VEQRLDLLQE QLNRLESQMT TDIQTILQLL QKQTTVVPPA YSMVTAGSEY
QRPIIQLMRT SQPEASIKTD RSFSPSSQCP EFLDLEKSKL KSKESLSSGV HLNTASEDNL
TSLLKQDSDL SLELHLRQRK TYVHPIRHPS LPDSSLSTVG IVGLHRHVSD PGLPGK
