KCNH4_HUMAN
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 03-AUG-2022, entry version 181.
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) (TC
CC 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; 8.
DR IntAct; Q9UQ05; 2.
DR STRING; 9606.ENSP00000264661; -.
DR ChEMBL; CHEMBL2362996; -.
DR DrugBank; DB00228; Enflurane.
DR DrugBank; DB01110; Miconazole.
DR DrugBank; DB01069; Promethazine.
DR DrugCentral; Q9UQ05; -.
DR GlyGen; Q9UQ05; 3 sites.
DR iPTMnet; Q9UQ05; -.
DR PhosphoSitePlus; Q9UQ05; -.
DR BioMuta; KCNH4; -.
DR DMDM; 26006815; -.
DR PaxDb; Q9UQ05; -.
DR PeptideAtlas; Q9UQ05; -.
DR PRIDE; Q9UQ05; -.
DR ProteomicsDB; 85484; -.
DR Antibodypedia; 53970; 82 antibodies from 12 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 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; NVCFLGD; -.
DR OrthoDB; 247304at2759; -.
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 1073 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 65 other tissues.
DR Genevisible; Q9UQ05; 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: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: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; 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 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
