KCNH3_HUMAN
ID KCNH3_HUMAN Reviewed; 1083 AA.
AC Q9ULD8; Q9UQ06;
DT 28-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT 28-NOV-2002, sequence version 2.
DT 03-AUG-2022, entry version 182.
DE RecName: Full=Potassium voltage-gated channel subfamily H member 3;
DE AltName: Full=Brain-specific eag-like channel 1;
DE Short=BEC1;
DE AltName: Full=Ether-a-go-go-like potassium channel 2;
DE Short=ELK channel 2;
DE Short=ELK2;
DE AltName: Full=Voltage-gated potassium channel subunit Kv12.2;
GN Name=KCNH3; Synonyms=KIAA1282;
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].
RC TISSUE=Brain;
RX PubMed=10455180; DOI=10.1074/jbc.274.35.25018;
RA Miyake A., Mochizuki S., Yokoi H., Kohda M., Furuichi K.;
RT "New ether-a-go-go K+ channel family members localized in human
RT telencephalon.";
RL J. Biol. Chem. 274:25018-25025(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=10574462; DOI=10.1093/dnares/6.5.337;
RA Nagase T., Ishikawa K., Kikuno R., Hirosawa M., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XV. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 6:337-345(1999).
CC -!- FUNCTION: Pore-forming (alpha) subunit of voltage-gated potassium
CC channel. Elicits an outward current with fast inactivation. Channel
CC properties may be modulated by cAMP and subunit 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.
CC -!- INTERACTION:
CC Q9ULD8; P04578: env; Xeno; NbExp=3; IntAct=EBI-8079227, EBI-6163496;
CC -!- SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein.
CC -!- TISSUE SPECIFICITY: Detected only in brain, in particular in the
CC telencephalon. Detected in the cerebral cortex, occipital pole, frontal
CC and temporal lobe, putamen, amygdala, hippocampus and caudate nucleus.
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. Kv12.2/KCNH3 sub-subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA86596.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AB022696; BAA83590.1; -; mRNA.
DR EMBL; AB033108; BAA86596.1; ALT_INIT; mRNA.
DR CCDS; CCDS8786.1; -.
DR RefSeq; NP_001300959.1; NM_001314030.1.
DR RefSeq; NP_036416.1; NM_012284.2.
DR AlphaFoldDB; Q9ULD8; -.
DR SMR; Q9ULD8; -.
DR BioGRID; 116988; 1.
DR IntAct; Q9ULD8; 4.
DR MINT; Q9ULD8; -.
DR STRING; 9606.ENSP00000257981; -.
DR ChEMBL; CHEMBL2363017; -.
DR DrugBank; DB00228; Enflurane.
DR DrugBank; DB01110; Miconazole.
DR DrugBank; DB01069; Promethazine.
DR DrugCentral; Q9ULD8; -.
DR GuidetoPHARMACOLOGY; 576; -.
DR TCDB; 1.A.1.20.5; the voltage-gated ion channel (vic) superfamily.
DR GlyGen; Q9ULD8; 3 sites.
DR iPTMnet; Q9ULD8; -.
DR PhosphoSitePlus; Q9ULD8; -.
DR BioMuta; KCNH3; -.
DR DMDM; 26006814; -.
DR jPOST; Q9ULD8; -.
DR MassIVE; Q9ULD8; -.
DR PaxDb; Q9ULD8; -.
DR PeptideAtlas; Q9ULD8; -.
DR PRIDE; Q9ULD8; -.
DR ProteomicsDB; 85003; -.
DR Antibodypedia; 25968; 99 antibodies from 20 providers.
DR DNASU; 23416; -.
DR Ensembl; ENST00000257981.7; ENSP00000257981.5; ENSG00000135519.8.
DR GeneID; 23416; -.
DR KEGG; hsa:23416; -.
DR MANE-Select; ENST00000257981.7; ENSP00000257981.5; NM_012284.3; NP_036416.1.
DR UCSC; uc001ruh.2; human.
DR CTD; 23416; -.
DR DisGeNET; 23416; -.
DR GeneCards; KCNH3; -.
DR HGNC; HGNC:6252; KCNH3.
DR HPA; ENSG00000135519; Group enriched (brain, pituitary gland).
DR MIM; 604527; gene.
DR neXtProt; NX_Q9ULD8; -.
DR OpenTargets; ENSG00000135519; -.
DR PharmGKB; PA30038; -.
DR VEuPathDB; HostDB:ENSG00000135519; -.
DR eggNOG; KOG0498; Eukaryota.
DR GeneTree; ENSGT00940000161742; -.
DR HOGENOM; CLU_005746_6_0_1; -.
DR InParanoid; Q9ULD8; -.
DR OMA; YIGQQEI; -.
DR OrthoDB; 247304at2759; -.
DR PhylomeDB; Q9ULD8; -.
DR TreeFam; TF313130; -.
DR PathwayCommons; Q9ULD8; -.
DR Reactome; R-HSA-1296072; Voltage gated Potassium channels.
DR SignaLink; Q9ULD8; -.
DR BioGRID-ORCS; 23416; 20 hits in 1072 CRISPR screens.
DR ChiTaRS; KCNH3; human.
DR GeneWiki; KCNH3; -.
DR GenomeRNAi; 23416; -.
DR Pharos; Q9ULD8; Tclin.
DR PRO; PR:Q9ULD8; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q9ULD8; protein.
DR Bgee; ENSG00000135519; Expressed in right frontal lobe and 118 other tissues.
DR ExpressionAtlas; Q9ULD8; baseline and differential.
DR Genevisible; Q9ULD8; HS.
DR GO; GO:0016021; C:integral component of membrane; NAS:UniProtKB.
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:0005249; F:voltage-gated potassium channel activity; IBA:GO_Central.
DR GO; GO:0071805; P:potassium ion transmembrane transport; IBA:GO_Central.
DR GO; GO:0006813; P:potassium ion transport; TAS:UniProtKB.
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; IPR003950; K_chnl_volt-dep_ELK.
DR InterPro; IPR001610; PAC.
DR InterPro; IPR000014; PAS.
DR InterPro; IPR000700; PAS-assoc_C.
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; PR01465; ELKCHANNEL.
DR SMART; SM00100; cNMP; 1.
DR SMART; SM00086; PAC; 1.
DR SUPFAM; SSF51206; SSF51206; 1.
DR SUPFAM; SSF55785; SSF55785; 1.
DR TIGRFAMs; TIGR00229; sensory_box; 1.
DR PROSITE; PS50042; CNMP_BINDING_3; 1.
DR PROSITE; PS50113; PAC; 1.
DR PROSITE; PS50112; PAS; 1.
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..1083
FT /note="Potassium voltage-gated channel subfamily H member
FT 3"
FT /id="PRO_0000054005"
FT TOPO_DOM 1..228
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 229..249
FT /note="Helical; Name=Segment S1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 250..259
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 260..280
FT /note="Helical; Name=Segment S2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 281..302
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 303..323
FT /note="Helical; Name=Segment S3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 324..331
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 332..352
FT /note="Helical; Voltage-sensor; Name=Segment S4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 353..361
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 362..382
FT /note="Helical; Name=Segment S5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 383..453
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT INTRAMEM 454..474
FT /note="Pore-forming; Name=Segment H5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 475..479
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 480..500
FT /note="Helical; Name=Segment S6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 501..1083
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 18..90
FT /note="PAS"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00140"
FT DOMAIN 93..145
FT /note="PAC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00141"
FT REGION 137..157
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 729..810
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 832..873
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 972..1055
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 465..470
FT /note="Selectivity filter"
FT /evidence="ECO:0000250"
FT COMPBIAS 137..154
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 753..768
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 839..859
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 984..1004
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 582..697
FT /ligand="a nucleoside 3',5'-cyclic phosphate"
FT /ligand_id="ChEBI:CHEBI:58464"
FT CARBOHYD 421
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 428
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 436
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 1083 AA; 117129 MW; EF35C8968D7418CC CRC64;
MPAMRGLLAP QNTFLDTIAT RFDGTHSNFV LGNAQVAGLF PVVYCSDGFC DLTGFSRAEV
MQRGCACSFL YGPDTSELVR QQIRKALDEH KEFKAELILY RKSGLPFWCL LDVIPIKNEK
GEVALFLVSH KDISETKNRG GPDRWKETGG GRRRYGRARS KGFNANRRRS RAVLYHLSGH
LQKQPKGKHK LNKGVFGEKP NLPEYKVAAI RKSPFILLHC GALRATWDGF ILLATLYVAV
TVPYSVCVST AREPSAARGP PSVCDLAVEV LFILDIVLNF RTTFVSKSGQ VVFAPKSICL
HYVTTWFLLD VIAALPFDLL HAFKVNVYFG AHLLKTVRLL RLLRLLPRLD RYSQYSAVVL
TLLMAVFALL AHWVACVWFY IGQREIESSE SELPEIGWLQ ELARRLETPY YLVGRRPAGG
NSSGQSDNCS SSSEANGTGL ELLGGPSLRS AYITSLYFAL SSLTSVGFGN VSANTDTEKI
FSICTMLIGA LMHAVVFGNV TAIIQRMYAR RFLYHSRTRD LRDYIRIHRI PKPLKQRMLE
YFQATWAVNN GIDTTELLQS LPDELRADIA MHLHKEVLQL PLFEAASRGC LRALSLALRP
AFCTPGEYLI HQGDALQALY FVCSGSMEVL KGGTVLAILG KGDLIGCELP RREQVVKANA
DVKGLTYCVL QCLQLAGLHD SLALYPEFAP RFSRGLRGEL SYNLGAGGGS AEVDTSSLSG
DNTLMSTLEE KETDGEQGPT VSPAPADEPS SPLLSPGCTS SSSAAKLLSP RRTAPRPRLG
GRGRPGRAGA LKAEAGPSAP PRALEGLRLP PMPWNVPPDL SPRVVDGIED GCGSDQPKFS
FRVGQSGPEC SSSPSPGPES GLLTVPHGPS EARNTDTLDK LRQAVTELSE QVLQMREGLQ
SLRQAVQLVL APHREGPCPR ASGEGPCPAS TSGLLQPLCV DTGASSYCLQ PPAGSVLSGT
WPHPRPGPPP LMAPWPWGPP ASQSSPWPRA TAFWTSTSDS EPPASGDLCS EPSTPASPPP
SEEGARTGPA EPVSQAEATS TGEPPPGSGG LALPWDPHSL EMVLIGCHGS GTVQWTQEEG
TGV
