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   24-JAN-2024, entry version 190.
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)
CC       (TC 1.A.1.20) subfamily. Kv11.3/KCNH7 sub-subfamily. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAD01946.1; Type=Frameshift; Evidence={ECO:0000305};
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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   DrugBank; DB03701; Vanoxerine.
DR   DrugCentral; Q9NS40; -.
DR   GlyCosmos; Q9NS40; 1 site, No reported glycans.
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; 9606-ENSP00000331727; -.
DR   PeptideAtlas; Q9NS40; -.
DR   ProteomicsDB; 82478; -. [Q9NS40-1]
DR   ProteomicsDB; 82479; -. [Q9NS40-2]
DR   ABCD; Q9NS40; 2 sequenced antibodies.
DR   Antibodypedia; 19119; 195 antibodies from 25 providers.
DR   DNASU; 90134; -.
DR   Ensembl; ENST00000328032.8; ENSP00000333781.4; ENSG00000184611.14. [Q9NS40-2]
DR   Ensembl; ENST00000332142.10; ENSP00000331727.5; ENSG00000184611.14. [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   AGR; HGNC:18863; -.
DR   CTD; 90134; -.
DR   DisGeNET; 90134; -.
DR   GeneCards; KCNH7; -.
DR   HGNC; HGNC:18863; KCNH7.
DR   HPA; ENSG00000184611; Tissue enhanced (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; MRTSHPV; -.
DR   OrthoDB; 66005at2759; -.
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; 10 hits in 1148 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 male germ line stem cell (sensu Vertebrata) in testis and 71 other cell types or tissues.
DR   ExpressionAtlas; Q9NS40; baseline and differential.
DR   GO; GO:0034702; C:monoatomic ion channel complex; IEA:UniProtKB-KW.
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: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   CDD; cd00038; CAP_ED; 1.
DR   CDD; cd00130; PAS; 1.
DR   Gene3D; 1.10.1200.260; -; 1.
DR   Gene3D; 1.10.287.70; -; 1.
DR   Gene3D; 2.60.120.10; Jelly Rolls; 1.
DR   Gene3D; 3.30.450.20; PAS domain; 1.
DR   InterPro; IPR000595; cNMP-bd_dom.
DR   InterPro; IPR018490; cNMP-bd_dom_sf.
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   NCBIfam; TIGR00229; sensory_box; 1.
DR   PANTHER; PTHR10217:SF466; POTASSIUM VOLTAGE-GATED CHANNEL SUBFAMILY H MEMBER 7; 1.
DR   PANTHER; PTHR10217; VOLTAGE AND LIGAND GATED POTASSIUM CHANNEL; 1.
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; cAMP-binding domain-like; 1.
DR   SUPFAM; SSF55785; PYP-like sensor domain (PAS domain); 1.
DR   SUPFAM; SSF81324; Voltage-gated potassium channels; 1.
DR   PROSITE; PS50042; CNMP_BINDING_3; 1.
DR   Genevisible; Q9NS40; HS.
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
//