ID   KCNH4_HUMAN             Reviewed;        1017 AA.
AC   Q9UQ05;
DT   28-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-2000, sequence version 1.
DT   27-MAR-2024, entry version 190.
DE   RecName: Full=Potassium voltage-gated channel subfamily H member 4;
DE   AltName: Full=Brain-specific eag-like channel 2;
DE            Short=BEC2;
DE   AltName: Full=Ether-a-go-go-like potassium channel 1;
DE            Short=ELK channel 1;
DE            Short=ELK1;
DE   AltName: Full=Voltage-gated potassium channel subunit Kv12.3;
GN   Name=KCNH4;
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   VARIANT [LARGE SCALE ANALYSIS] ARG-797.
RX   PubMed=16959974; DOI=10.1126/science.1133427;
RA   Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA   Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA   Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA   Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA   Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA   Velculescu V.E.;
RT   "The consensus coding sequences of human breast and colorectal cancers.";
RL   Science 314:268-274(2006).
CC   -!- FUNCTION: Pore-forming (alpha) subunit of voltage-gated potassium
CC       channel. Elicits an outward current, but shows no 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   -!- SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein.
CC   -!- TISSUE SPECIFICITY: Detected only in brain, in particular in the
CC       telencephalon. Detected in putamen and caudate nucleus, and at lower
CC       levels in cerebral cortex, occipital and hippocampus.
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. Kv12.3/KCNH4 sub-subfamily. {ECO:0000305}.
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DR   EMBL; AB022698; BAA83592.1; -; mRNA.
DR   CCDS; CCDS11420.1; -.
DR   RefSeq; NP_036417.1; NM_012285.2.
DR   RefSeq; XP_016879889.1; XM_017024400.1.
DR   AlphaFoldDB; Q9UQ05; -.
DR   SMR; Q9UQ05; -.
DR   BioGRID; 116987; 14.
DR   IntAct; Q9UQ05; 1.
DR   STRING; 9606.ENSP00000264661; -.
DR   ChEMBL; CHEMBL2362996; -.
DR   DrugBank; DB00228; Enflurane.
DR   DrugBank; DB01110; Miconazole.
DR   DrugBank; DB01069; Promethazine.
DR   DrugCentral; Q9UQ05; -.
DR   GlyCosmos; Q9UQ05; 3 sites, No reported glycans.
DR   GlyGen; Q9UQ05; 3 sites.
DR   iPTMnet; Q9UQ05; -.
DR   PhosphoSitePlus; Q9UQ05; -.
DR   BioMuta; KCNH4; -.
DR   DMDM; 26006815; -.
DR   MassIVE; Q9UQ05; -.
DR   PaxDb; 9606-ENSP00000264661; -.
DR   PeptideAtlas; Q9UQ05; -.
DR   ProteomicsDB; 85484; -.
DR   Pumba; Q9UQ05; -.
DR   Antibodypedia; 53970; 92 antibodies from 14 providers.
DR   DNASU; 23415; -.
DR   Ensembl; ENST00000264661.4; ENSP00000264661.2; ENSG00000089558.9.
DR   Ensembl; ENST00000607371.5; ENSP00000475564.1; ENSG00000089558.9.
DR   GeneID; 23415; -.
DR   KEGG; hsa:23415; -.
DR   MANE-Select; ENST00000264661.4; ENSP00000264661.2; NM_012285.3; NP_036417.1.
DR   UCSC; uc002hzb.3; human.
DR   AGR; HGNC:6253; -.
DR   CTD; 23415; -.
DR   DisGeNET; 23415; -.
DR   GeneCards; KCNH4; -.
DR   HGNC; HGNC:6253; KCNH4.
DR   HPA; ENSG00000089558; Tissue enriched (brain).
DR   MIM; 604528; gene.
DR   neXtProt; NX_Q9UQ05; -.
DR   OpenTargets; ENSG00000089558; -.
DR   PharmGKB; PA30039; -.
DR   VEuPathDB; HostDB:ENSG00000089558; -.
DR   eggNOG; KOG0498; Eukaryota.
DR   GeneTree; ENSGT00940000156363; -.
DR   HOGENOM; CLU_005746_6_0_1; -.
DR   InParanoid; Q9UQ05; -.
DR   OMA; MEGLCRY; -.
DR   OrthoDB; 66005at2759; -.
DR   PhylomeDB; Q9UQ05; -.
DR   TreeFam; TF313130; -.
DR   PathwayCommons; Q9UQ05; -.
DR   Reactome; R-HSA-1296072; Voltage gated Potassium channels.
DR   SignaLink; Q9UQ05; -.
DR   BioGRID-ORCS; 23415; 19 hits in 1151 CRISPR screens.
DR   ChiTaRS; KCNH4; human.
DR   GeneWiki; KCNH4; -.
DR   GenomeRNAi; 23415; -.
DR   Pharos; Q9UQ05; Tclin.
DR   PRO; PR:Q9UQ05; -.
DR   Proteomes; UP000005640; Chromosome 17.
DR   RNAct; Q9UQ05; Protein.
DR   Bgee; ENSG00000089558; Expressed in putamen and 67 other cell types or tissues.
DR   GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR   GO; GO:0008076; C:voltage-gated potassium channel complex; TAS:ProtInc.
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:ProtInc.
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; 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; 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   NCBIfam; TIGR00229; sensory_box; 1.
DR   PANTHER; PTHR10217:SF630; POTASSIUM VOLTAGE-GATED CHANNEL SUBFAMILY H MEMBER 4; 1.
DR   PANTHER; PTHR10217; VOLTAGE AND LIGAND GATED POTASSIUM CHANNEL; 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; 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   PROSITE; PS50113; PAC; 1.
DR   PROSITE; PS50112; PAS; 1.
DR   Genevisible; Q9UQ05; HS.
PE   2: Evidence at transcript 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..1017
FT                   /note="Potassium voltage-gated channel subfamily H member
FT                   4"
FT                   /id="PRO_0000054008"
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..332
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        333..353
FT                   /note="Helical; Voltage-sensor; Name=Segment S4"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        354..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..427
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   INTRAMEM        428..448
FT                   /note="Pore-forming; Name=Segment H5"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        449..482
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        483..503
FT                   /note="Helical; Name=Segment S6"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        504..1017
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          14..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          138..157
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          691..749
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          772..803
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          821..875
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          971..1017
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           439..444
FT                   /note="Selectivity filter"
FT                   /evidence="ECO:0000250"
FT   COMPBIAS        691..725
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        772..788
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        979..1000
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1003..1017
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   BINDING         556..671
FT                   /ligand="a nucleoside 3',5'-cyclic phosphate"
FT                   /ligand_id="ChEBI:CHEBI:58464"
FT   CARBOHYD        326
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        414
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        473
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   VARIANT         797
FT                   /note="G -> R (in a colorectal cancer sample; somatic
FT                   mutation)"
FT                   /evidence="ECO:0000269|PubMed:16959974"
FT                   /id="VAR_035771"
SQ   SEQUENCE   1017 AA;  111693 MW;  4B480DFC75816A38 CRC64;
     MPVMKGLLAP QNTFLDTIAT RFDGTHSNFL LANAQGTRGF PIVYCSDGFC ELTGYGRTEV
     MQKTCSCRFL YGPETSEPAL QRLHKALEGH QEHRAEICFY RKDGSAFWCL LDMMPIKNEM
     GEVVLFLFSF KDITQSGSPG LGPQGGRGDS NHENSLGRRG ATWKFRSARR RSRTVLHRLT
     GHFGRRGQGG MKANNNVFEP KPSVPEYKVA SVGGSRCLLL HYSVSKAIWD GLILLATFYV
     AVTVPYNVCF SGDDDTPITS RHTLVSDIAV EMLFILDIIL NFRTTYVSQS GQVISAPRSI
     GLHYLATWFF IDLIAALPFD LLYIFNITVT SLVHLLKTVR LLRLLRLLQK LERYSQCSAV
     VLTLLMSVFA LLAHWMACIW YVIGRREMEA NDPLLWDIGW LHELGKRLEV PYVNGSVGGP
     SRRSAYIAAL YFTLSSLTSV GFGNVCANTD AEKIFSICTM LIGALMHAVV FGNVTAIIQR
     MYSRRSLYHS RMKDLKDFIR VHRLPRPLKQ RMLEYFQTTW AVNSGIDANE LLRDFPDELR
     ADIAMHLNRE ILQLPLFGAA SRGCLRALSL HIKTSFCAPG EYLLRRGDAL QAHYYVCSGS
     LEVLRDNMVL AILGKGDLIG ADIPEPGQEP GLGADPNFVL KTSADVKALT YCGLQQLSSR
     GLAEVLRLYP EYGAAFRAGL PRDLTFNLRQ GSDTSGLSRF SRSPRLSQPR SESLGSSSDK
     TLPSITEAES GAEPGGGPRP RRPLLLPNLS PARPRGSLVS LLGEELPPFS ALVSSPSLSP
     SLSPALAGQG HSASPHGPPR CSAAWKPPQL LIPPLGTFGP PDLSPRIVDG IEDSGSTAEA
     PSFRFSRRPE LPRPRSQAPP TGTRPSPELA SEAEEVKEKV CRLNQEISRL NQEVSQLSRE
     LRHIMGLLQA RLGPPGHPAG SAWTPDPPCP QLRPPCLSPC ASRPPPSLQD TTLAEVHCPA
     SVGTMETGTA LLDLRPSILP PYPSEPDPLG PSPVPEASPP TPSLLRHSFQ SRSDTFH
//