KCNH8_HUMAN
ID KCNH8_HUMAN Reviewed; 1107 AA.
AC Q96L42; B7Z2I7; Q59GQ6;
DT 28-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT 05-MAY-2009, sequence version 2.
DT 03-AUG-2022, entry version 177.
DE RecName: Full=Potassium voltage-gated channel subfamily H member 8;
DE AltName: Full=ELK1;
DE Short=hElk1;
DE AltName: Full=Ether-a-go-go-like potassium channel 3;
DE Short=ELK channel 3;
DE Short=ELK3;
DE AltName: Full=Voltage-gated potassium channel subunit Kv12.1;
GN Name=KCNH8;
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), AND VARIANT ARG-893.
RC TISSUE=Brain;
RX PubMed=11897058; DOI=10.1177/108705710200700110;
RA Baxter D.F., Kirk M., Garcia A.F., Raimondi A., Holmqvist M.H., Flint K.K.,
RA Bojanic D., DiStefano P.S., Curtis R., Xie Y.;
RT "A novel membrane potential-sensitive fluorescent dye improves cell-based
RT assays for ion channels.";
RL J. Biomol. Screen. 7:79-85(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain;
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 GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J.,
RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X.,
RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 525-1107 (ISOFORM 1).
RC TISSUE=Brain;
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.,
RA Ohara O., Nagase T., Kikuno R.F.;
RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP TISSUE SPECIFICITY.
RX PubMed=12890647; DOI=10.1152/ajpcell.00179.2003;
RA Zou A., Lin Z., Humble M., Creech C.D., Wagoner P.K., Krafte D.,
RA Jegla T.J., Wickenden A.D.;
RT "Distribution and functional properties of human KCNH8 (Elk1) potassium
RT channels.";
RL Am. J. Physiol. 285:C1356-C1366(2003).
CC -!- FUNCTION: Pore-forming (alpha) subunit of voltage-gated potassium
CC channel. Elicits a slowly activating, outward rectifying current.
CC Channel 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 -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q96L42-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q96L42-2; Sequence=VSP_057036, VSP_057037, VSP_057038,
CC VSP_057039;
CC -!- TISSUE SPECIFICITY: Primarily expressed in the nervous system.
CC {ECO:0000269|PubMed:12890647}.
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. Kv12.1/KCNH8 sub-subfamily. {ECO:0000305}.
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DR EMBL; AY053503; AAL15429.1; -; mRNA.
DR EMBL; AK294759; BAH11873.1; -; mRNA.
DR EMBL; AC015542; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC061958; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC099538; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC116098; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC135452; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC138315; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AB209053; BAD92290.1; -; mRNA.
DR CCDS; CCDS2632.1; -. [Q96L42-1]
DR RefSeq; NP_653234.2; NM_144633.2. [Q96L42-1]
DR AlphaFoldDB; Q96L42; -.
DR SMR; Q96L42; -.
DR BioGRID; 126271; 1.
DR ELM; Q96L42; -.
DR IntAct; Q96L42; 2.
DR STRING; 9606.ENSP00000328813; -.
DR ChEMBL; CHEMBL2362996; -.
DR DrugBank; DB00228; Enflurane.
DR DrugBank; DB01110; Miconazole.
DR DrugBank; DB01069; Promethazine.
DR DrugCentral; Q96L42; -.
DR GuidetoPHARMACOLOGY; 575; -.
DR GlyGen; Q96L42; 2 sites.
DR iPTMnet; Q96L42; -.
DR PhosphoSitePlus; Q96L42; -.
DR BioMuta; KCNH8; -.
DR DMDM; 229462927; -.
DR MassIVE; Q96L42; -.
DR PaxDb; Q96L42; -.
DR PeptideAtlas; Q96L42; -.
DR PRIDE; Q96L42; -.
DR Antibodypedia; 11263; 77 antibodies from 17 providers.
DR DNASU; 131096; -.
DR Ensembl; ENST00000328405.7; ENSP00000328813.2; ENSG00000183960.9. [Q96L42-1]
DR GeneID; 131096; -.
DR KEGG; hsa:131096; -.
DR MANE-Select; ENST00000328405.7; ENSP00000328813.2; NM_144633.3; NP_653234.2.
DR UCSC; uc003cbk.2; human. [Q96L42-1]
DR CTD; 131096; -.
DR DisGeNET; 131096; -.
DR GeneCards; KCNH8; -.
DR HGNC; HGNC:18864; KCNH8.
DR HPA; ENSG00000183960; Tissue enhanced (brain, pituitary gland).
DR MIM; 608260; gene.
DR neXtProt; NX_Q96L42; -.
DR OpenTargets; ENSG00000183960; -.
DR PharmGKB; PA38724; -.
DR VEuPathDB; HostDB:ENSG00000183960; -.
DR eggNOG; KOG0498; Eukaryota.
DR GeneTree; ENSGT00940000156869; -.
DR HOGENOM; CLU_005746_6_0_1; -.
DR InParanoid; Q96L42; -.
DR OMA; MEQNNPL; -.
DR OrthoDB; 247304at2759; -.
DR PhylomeDB; Q96L42; -.
DR TreeFam; TF313130; -.
DR PathwayCommons; Q96L42; -.
DR Reactome; R-HSA-1296072; Voltage gated Potassium channels.
DR SignaLink; Q96L42; -.
DR BioGRID-ORCS; 131096; 11 hits in 1071 CRISPR screens.
DR ChiTaRS; KCNH8; human.
DR GeneWiki; KCNH8; -.
DR GenomeRNAi; 131096; -.
DR Pharos; Q96L42; Tclin.
DR PRO; PR:Q96L42; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q96L42; protein.
DR Bgee; ENSG00000183960; Expressed in corpus callosum and 109 other tissues.
DR ExpressionAtlas; Q96L42; baseline and differential.
DR Genevisible; Q96L42; HS.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
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: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.
PE 2: Evidence at transcript 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..1107
FT /note="Potassium voltage-gated channel subfamily H member
FT 8"
FT /id="PRO_0000054018"
FT TOPO_DOM 1..225
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 226..246
FT /note="Helical; Name=Segment S1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 247..255
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 256..276
FT /note="Helical; Name=Segment S2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 277..298
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 299..319
FT /note="Helical; Name=Segment S3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 320..327
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 328..348
FT /note="Helical; Voltage-sensor; Name=Segment S4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 349..357
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 358..378
FT /note="Helical; Name=Segment S5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 379..419
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT INTRAMEM 420..440
FT /note="Pore-forming; Name=Segment H5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 441..448
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 449..469
FT /note="Helical; Name=Segment S6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 470..1107
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 18..90
FT /note="PAS"
FT DOMAIN 93..145
FT /note="PAC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00141"
FT REGION 686..742
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 764..791
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 818..847
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 961..989
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 434..439
FT /note="Selectivity filter"
FT /evidence="ECO:0000250"
FT COMPBIAS 686..701
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 765..780
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 551..668
FT /ligand="a nucleoside 3',5'-cyclic phosphate"
FT /ligand_id="ChEBI:CHEBI:58464"
FT CARBOHYD 320
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 409
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 1..359
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_057036"
FT VAR_SEQ 459
FT /note="A -> VSQFQVCPRPSWIICWFRNHFGFILLMTT (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_057037"
FT VAR_SEQ 515..516
FT /note="WS -> CF (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_057038"
FT VAR_SEQ 517..1107
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_057039"
FT VARIANT 893
FT /note="Q -> R (in dbSNP:rs33915638)"
FT /evidence="ECO:0000269|PubMed:11897058"
FT /id="VAR_055098"
FT VARIANT 984
FT /note="E -> Q (in dbSNP:rs35160416)"
FT /id="VAR_055099"
FT CONFLICT 525
FT /note="E -> Q (in Ref. 4; BAD92290)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1107 AA; 123804 MW; F0E5DEC9A7877869 CRC64;
MPVMKGLLAP QNTFLDTIAT RFDGTHSNFI LANAQVAKGF PIVYCSDGFC ELAGFARTEV
MQKSCSCKFL FGVETNEQLM LQIEKSLEEK TEFKGEIMFY KKNGSPFWCL LDIVPIKNEK
GDVVLFLASF KDITDTKVKI TPEDKKEDKV KGRSRAGTHF DSARRRSRAV LYHISGHLQR
REKNKLKINN NVFVDKPAFP EYKVSDAKKS KFILLHFSTF KAGWDWLILL ATFYVAVTVP
YNVCFIGNDD LSTTRSTTVS DIAVEILFII DIILNFRTTY VSKSGQVIFE ARSICIHYVT
TWFIIDLIAA LPFDLLYAFN VTVVSLVHLL KTVRLLRLLR LLQKLDRYSQ HSTIVLTLLM
SMFALLAHWM ACIWYVIGKM EREDNSLLKW EVGWLHELGK RLESPYYGNN TLGGPSIRSA
YIAALYFTLS SLTSVGFGNV SANTDAEKIF SICTMLIGAL MHALVFGNVT AIIQRMYSRW
SLYHTRTKDL KDFIRVHHLP QQLKQRMLEY FQTTWSVNNG IDSNELLKDF PDELRSDITM
HLNKEILQLS LFECASRGCL RSLSLHIKTS FCAPGEYLLR QGDALQAIYF VCSGSMEVLK
DSMVLAILGK GDLIGANLSI KDQVIKTNAD VKALTYCDLQ CIILKGLFEV LDLYPEYAHK
FVEDIQHDLT YNLREGHESD VISRLSNKSM VSQSEPKGNG NINKRLPSIV EDEEEEEEGE
EEEAVSLSPI CTRGSSSRNK KVGSNKAYLG LSLKQLASGT VPFHSPIRVS RSNSPKTKQE
IDPPNHNKRK EKNLKLQLST LNNAGPPDLS PRIVDGIEDG NSSEESQTFD FGSERIRSEP
RISPPLGDPE IGAAVLFIKA EETKQQINKL NSEVTTLTQE VSQLGKDMRN VIQLLENVLS
PQQPSRFCSL HSTSVCPSRE SLQTRTSWSA HQPCLHLQTG GAAYTQAQLC SSNITSDIWS
VDPSSVGSSP QRTGAHEQNP ADSELYHSPS LDYSPSHYQV VQEGHLQFLR CISPHSDSTL
TPLQSISATL SSSVCSSSET SLHLVLPSRS EEGSFSQGTV SSFSLENLPG SWNQEGMASA
STKPLENLPL EVVTSTAEVK DNKAINV
