KCNH6_HUMAN
ID KCNH6_HUMAN Reviewed; 994 AA.
AC Q9H252; Q9BRD7;
DT 28-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 186.
DE RecName: Full=Potassium voltage-gated channel subfamily H member 6;
DE AltName: Full=Ether-a-go-go-related gene potassium channel 2;
DE Short=ERG-2;
DE Short=Eag-related protein 2;
DE Short=Ether-a-go-go-related protein 2;
DE Short=hERG-2;
DE Short=hERG2;
DE AltName: Full=Voltage-gated potassium channel subunit Kv11.2;
GN Name=KCNH6; Synonyms=ERG2;
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 Titus S.A., Ganetzky B.S.;
RT "Human Eag-related gene member 2 (Herg2) potassium channel.";
RL Submitted (OCT-2000) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT MET-925.
RC TISSUE=Amygdala, and Kidney;
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 MRNA] (ISOFORM 3).
RC TISSUE=Uterus;
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).
RN [5]
RP GLYCOSYLATION AT ASN-449.
RX PubMed=19139490; DOI=10.1074/mcp.m800504-mcp200;
RA Jia W., Lu Z., Fu Y., Wang H.P., Wang L.H., Chi H., Yuan Z.F., Zheng Z.B.,
RA Song L.N., Han H.H., Liang Y.M., Wang J.L., Cai Y., Zhang Y.K., Deng Y.L.,
RA Ying W.T., He S.M., Qian X.H.;
RT "A strategy for precise and large scale identification of core fucosylated
RT glycoproteins.";
RL Mol. Cell. Proteomics 8:913-923(2009).
CC -!- FUNCTION: Pore-forming (alpha) subunit of voltage-gated potassium
CC channel. Elicits a slowly activating, rectifying current (By
CC similarity). Channel properties may be modulated by cAMP and subunit
CC assembly. {ECO:0000250}.
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. Heteromultimers with
CC KCNH2/ERG1 and KCNH7/ERG3 (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Comment=Experimental confirmation may be lacking for some isoforms.;
CC Name=1;
CC IsoId=Q9H252-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9H252-2; Sequence=VSP_000977, VSP_000978;
CC Name=3;
CC IsoId=Q9H252-3; Sequence=VSP_000979, VSP_000980;
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. Kv11.2/KCNH6 sub-subfamily. {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; AF311913; AAG40871.1; -; mRNA.
DR EMBL; AK090969; BAC03559.1; -; mRNA.
DR EMBL; AK091877; BAC03764.1; -; mRNA.
DR EMBL; BC006334; AAH06334.1; -; mRNA.
DR CCDS; CCDS11638.1; -. [Q9H252-1]
DR CCDS; CCDS11639.1; -. [Q9H252-2]
DR RefSeq; NP_001265848.1; NM_001278919.1.
DR RefSeq; NP_001265849.1; NM_001278920.1.
DR RefSeq; NP_110406.1; NM_030779.3. [Q9H252-1]
DR RefSeq; NP_775115.1; NM_173092.2. [Q9H252-2]
DR RefSeq; XP_011523612.1; XM_011525310.2. [Q9H252-2]
DR RefSeq; XP_016880664.1; XM_017025175.1. [Q9H252-1]
DR AlphaFoldDB; Q9H252; -.
DR SMR; Q9H252; -.
DR STRING; 9606.ENSP00000463533; -.
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; Q9H252; -.
DR GuidetoPHARMACOLOGY; 573; -.
DR GlyGen; Q9H252; 1 site.
DR iPTMnet; Q9H252; -.
DR PhosphoSitePlus; Q9H252; -.
DR BioMuta; KCNH6; -.
DR DMDM; 26006810; -.
DR jPOST; Q9H252; -.
DR MassIVE; Q9H252; -.
DR PaxDb; Q9H252; -.
DR PeptideAtlas; Q9H252; -.
DR PRIDE; Q9H252; -.
DR ProteomicsDB; 80495; -. [Q9H252-1]
DR ProteomicsDB; 80496; -. [Q9H252-2]
DR ProteomicsDB; 80497; -. [Q9H252-3]
DR Antibodypedia; 18667; 140 antibodies from 29 providers.
DR DNASU; 81033; -.
DR Ensembl; ENST00000456941.6; ENSP00000396900.2; ENSG00000173826.15. [Q9H252-2]
DR Ensembl; ENST00000580652.5; ENSP00000464672.1; ENSG00000173826.15. [Q9H252-3]
DR Ensembl; ENST00000581784.5; ENSP00000463830.1; ENSG00000173826.15. [Q9H252-2]
DR Ensembl; ENST00000583023.1; ENSP00000463533.1; ENSG00000173826.15. [Q9H252-1]
DR GeneID; 81033; -.
DR KEGG; hsa:81033; -.
DR UCSC; uc002jax.2; human. [Q9H252-1]
DR CTD; 81033; -.
DR DisGeNET; 81033; -.
DR GeneCards; KCNH6; -.
DR HGNC; HGNC:18862; KCNH6.
DR HPA; ENSG00000173826; Tissue enhanced (intestine, kidney, pituitary gland, prostate, retina).
DR MIM; 608168; gene.
DR neXtProt; NX_Q9H252; -.
DR OpenTargets; ENSG00000173826; -.
DR PharmGKB; PA38722; -.
DR VEuPathDB; HostDB:ENSG00000173826; -.
DR eggNOG; KOG0498; Eukaryota.
DR GeneTree; ENSGT00940000157790; -.
DR HOGENOM; CLU_005746_2_3_1; -.
DR InParanoid; Q9H252; -.
DR OrthoDB; 247304at2759; -.
DR PhylomeDB; Q9H252; -.
DR TreeFam; TF313130; -.
DR PathwayCommons; Q9H252; -.
DR Reactome; R-HSA-1296072; Voltage gated Potassium channels.
DR BioGRID-ORCS; 81033; 5 hits in 1068 CRISPR screens.
DR GeneWiki; KCNH6; -.
DR GenomeRNAi; 81033; -.
DR Pharos; Q9H252; Tclin.
DR PRO; PR:Q9H252; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q9H252; protein.
DR Bgee; ENSG00000173826; Expressed in buccal mucosa cell and 68 other tissues.
DR ExpressionAtlas; Q9H252; baseline and differential.
DR Genevisible; Q9H252; 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:0005249; F:voltage-gated potassium channel activity; IBA:GO_Central.
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:0086091; P:regulation of heart rate by cardiac conduction; 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 GO; GO:0060307; P:regulation of ventricular cardiac muscle cell membrane repolarization; 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; IPR030172; KCNH6.
DR InterPro; IPR000014; PAS.
DR InterPro; IPR035965; PAS-like_dom_sf.
DR InterPro; IPR014710; RmlC-like_jellyroll.
DR PANTHER; PTHR10217:SF468; PTHR10217:SF468; 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; SSF51206; 1.
DR SUPFAM; SSF55785; SSF55785; 1.
DR PROSITE; PS50042; CNMP_BINDING_3; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; 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..994
FT /note="Potassium voltage-gated channel subfamily H member
FT 6"
FT /id="PRO_0000054013"
FT TOPO_DOM 1..261
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 262..282
FT /note="Helical; Name=Segment S1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 283..298
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 299..319
FT /note="Helical; Name=Segment S2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 320..340
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 341..361
FT /note="Helical; Name=Segment S3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 362..370
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 371..391
FT /note="Helical; Voltage-sensor; Name=Segment S4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 392..398
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 399..419
FT /note="Helical; Name=Segment S5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 420..463
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT INTRAMEM 464..484
FT /note="Pore-forming; Name=Segment H5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 485..490
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 491..511
FT /note="Helical; Name=Segment S6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 512..994
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 41..70
FT /note="PAS"
FT DOMAIN 92..144
FT /note="PAC"
FT REGION 720..790
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 880..946
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 476..481
FT /note="Selectivity filter"
FT /evidence="ECO:0000250"
FT COMPBIAS 725..750
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 594..711
FT /ligand="a nucleoside 3',5'-cyclic phosphate"
FT /ligand_id="ChEBI:CHEBI:58464"
FT CARBOHYD 449
FT /note="N-linked (GlcNAc...) (complex) asparagine"
FT /evidence="ECO:0000269|PubMed:19139490"
FT VAR_SEQ 419..472
FT /note="WYAIGNVERPYLEHKIGWLDSLGVQLGKRYNGSDPASGPSVQDKYVTALYFT
FT FS -> C (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_000977"
FT VAR_SEQ 501..502
FT /note="SL -> CE (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_000979"
FT VAR_SEQ 503..994
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_000980"
FT VAR_SEQ 745..780
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_000978"
FT VARIANT 165
FT /note="G -> R (in dbSNP:rs35399062)"
FT /id="VAR_053857"
FT VARIANT 925
FT /note="T -> M (in dbSNP:rs35819807)"
FT /evidence="ECO:0000269|PubMed:14702039"
FT /id="VAR_053858"
FT CONFLICT 963
FT /note="F -> L (in Ref. 2; BAC03764)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 994 AA; 109925 MW; BE9ECB349A798576 CRC64;
MPVRRGHVAP QNTYLDTIIR KFEGQSRKFL IANAQMENCA IIYCNDGFCE LFGYSRVEVM
QQPCTCDFLT GPNTPSSAVS RLAQALLGAE ECKVDILYYR KDASSFRCLV DVVPVKNEDG
AVIMFILNFE DLAQLLAKCS SRSLSQRLLS QSFLGSEGSH GRPGGPGPGT GRGKYRTISQ
IPQFTLNFVE FNLEKHRSSS TTEIEIIAPH KVVERTQNVT EKVTQVLSLG ADVLPEYKLQ
APRIHRWTIL HYSPFKAVWD WLILLLVIYT AVFTPYSAAF LLSDQDESRR GACSYTCSPL
TVVDLIVDIM FVVDIVINFR TTYVNTNDEV VSHPRRIAVH YFKGWFLIDM VAAIPFDLLI
FRTGSDETTT LIGLLKTARL LRLVRVARKL DRYSEYGAAV LFLLMCTFAL IAHWLACIWY
AIGNVERPYL EHKIGWLDSL GVQLGKRYNG SDPASGPSVQ DKYVTALYFT FSSLTSVGFG
NVSPNTNSEK VFSICVMLIG SLMYASIFGN VSAIIQRLYS GTARYHTQML RVKEFIRFHQ
IPNPLRQRLE EYFQHAWSYT NGIDMNAVLK GFPECLQADI CLHLHRALLQ HCPAFSGAGK
GCLRALAVKF KTTHAPPGDT LVHLGDVLST LYFISRGSIE ILRDDVVVAI LGKNDIFGEP
VSLHAQPGKS SADVRALTYC DLHKIQRADL LEVLDMYPAF AESFWSKLEV TFNLRDAAGG
LHSSPRQAPG SQDHQGFFLS DNQSGSPHEL GPQFPSKGYS LLGPGSQNSM GAGPCAPGHP
DAAPPLSISD ASGLWPELLQ EMPPRHSPQS PQEDPDCWPL KLGSRLEQLQ AQMNRLESRV
SSDLSRILQL LQKPMPQGHA SYILEAPASN DLALVPIASE TTSPGPRLPQ GFLPPAQTPS
YGDLDDCSPK HRNSSPRMPH LAVATDKTLA PSSEQEQPEG LWPPLASPLH PLEVQGLICG
PCFSSLPEHL GSVPKQLDFQ RHGSDPGFAG SWGH
