KCNA6_HUMAN
ID KCNA6_HUMAN Reviewed; 529 AA.
AC P17658;
DT 01-AUG-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1990, sequence version 1.
DT 03-AUG-2022, entry version 190.
DE RecName: Full=Potassium voltage-gated channel subfamily A member 6;
DE AltName: Full=Voltage-gated potassium channel HBK2 {ECO:0000303|PubMed:2347305};
DE AltName: Full=Voltage-gated potassium channel subunit Kv1.6;
GN Name=KCNA6;
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], FUNCTION, AND SUBCELLULAR LOCATION.
RC TISSUE=Brain;
RX PubMed=2347305; DOI=10.1002/j.1460-2075.1990.tb08299.x;
RA Grupe A., Schroeter K.H., Ruppersberg J.P., Stocker M., Drewes T.,
RA Beckh S., Pongs O.;
RT "Cloning and expression of a human voltage-gated potassium channel. A novel
RT member of the RCK potassium channel family.";
RL EMBO J. 9:1749-1756(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [3]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=14575698; DOI=10.1016/j.bbrc.2003.09.167;
RA Guihard G., Bellocq C., Grelet E., Escande D.;
RT "Human Kv1.6 current displays a C-type-like inactivation when re-expressed
RT in cos-7 cells.";
RL Biochem. Biophys. Res. Commun. 311:83-89(2003).
CC -!- FUNCTION: Voltage-gated potassium channel that mediates transmembrane
CC potassium transport in excitable membranes. Forms tetrameric potassium-
CC selective channels through which potassium ions pass in accordance with
CC their electrochemical gradient (PubMed:2347305, PubMed:14575698). The
CC channel alternates between opened and closed conformations in response
CC to the voltage difference across the membrane (PubMed:2347305,
CC PubMed:14575698). Can form functional homotetrameric channels and
CC heterotetrameric channels that contain variable proportions of KCNA1,
CC KCNA2, KCNA4, KCNA6, and possibly other family members as well; channel
CC properties depend on the type of alpha subunits that are part of the
CC channel (By similarity). Channel properties are modulated by
CC cytoplasmic beta subunits that regulate the subcellular location of the
CC alpha subunits and promote rapid inactivation (By similarity).
CC Homotetrameric channels display rapid activation and slow inactivation
CC (PubMed:2347305). {ECO:0000250|UniProtKB:P17659,
CC ECO:0000269|PubMed:14575698, ECO:0000269|PubMed:2347305}.
CC -!- SUBUNIT: Homotetramer and heterotetramer of potassium channel proteins
CC (By similarity). Interacts with KCNAB1 and KCNAB2 (By similarity).
CC {ECO:0000250|UniProtKB:P17659, ECO:0000305}.
CC -!- INTERACTION:
CC P17658; Q9UPQ8: DOLK; NbExp=4; IntAct=EBI-6426142, EBI-8645574;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:14575698,
CC ECO:0000269|PubMed:2347305}; Multi-pass membrane protein {ECO:0000305}.
CC -!- DOMAIN: The N-terminus may be important in determining the rate of
CC inactivation of the channel while the tail may play a role in
CC modulation of channel activity and/or targeting of the channel to
CC specific subcellular compartments.
CC -!- DOMAIN: The transmembrane segment S4 functions as voltage-sensor and is
CC characterized by a series of positively charged amino acids at every
CC third position. Channel opening and closing is effected by a
CC conformation change that affects the position and orientation of the
CC voltage-sensor paddle formed by S3 and S4 within the membrane. A
CC transmembrane electric field that is positive inside would push the
CC positively charged S4 segment outwards, thereby opening the pore, while
CC a field that is negative inside would pull the S4 segment inwards and
CC close the pore. Changes in the position and orientation of S4 are then
CC transmitted to the activation gate formed by the inner helix bundle via
CC the S4-S5 linker region. {ECO:0000250|UniProtKB:P63142}.
CC -!- SIMILARITY: Belongs to the potassium channel family. A (Shaker) (TC
CC 1.A.1.2) subfamily. Kv1.6/KCNA6 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; X17622; CAA35623.1; -; mRNA.
DR EMBL; BC069355; AAH69355.1; -; mRNA.
DR CCDS; CCDS8534.1; -.
DR PIR; S12787; S12787.
DR RefSeq; NP_002226.1; NM_002235.3.
DR RefSeq; XP_005253743.1; XM_005253686.3.
DR RefSeq; XP_011519257.1; XM_011520955.2.
DR RefSeq; XP_016874759.1; XM_017019270.1.
DR RefSeq; XP_016874760.1; XM_017019271.1.
DR RefSeq; XP_016874761.1; XM_017019272.1.
DR AlphaFoldDB; P17658; -.
DR SMR; P17658; -.
DR BioGRID; 109944; 18.
DR IntAct; P17658; 5.
DR STRING; 9606.ENSP00000280684; -.
DR BindingDB; P17658; -.
DR ChEMBL; CHEMBL5279; -.
DR DrugBank; DB06637; Dalfampridine.
DR DrugBank; DB00228; Enflurane.
DR DrugBank; DB01110; Miconazole.
DR DrugBank; DB01069; Promethazine.
DR DrugCentral; P17658; -.
DR GuidetoPHARMACOLOGY; 543; -.
DR TCDB; 1.A.1.2.29; the voltage-gated ion channel (vic) superfamily.
DR iPTMnet; P17658; -.
DR PhosphoSitePlus; P17658; -.
DR BioMuta; HGNC:6225; -.
DR DMDM; 116434; -.
DR MassIVE; P17658; -.
DR PaxDb; P17658; -.
DR PeptideAtlas; P17658; -.
DR PRIDE; P17658; -.
DR ProteomicsDB; 53501; -.
DR ABCD; P17658; 1 sequenced antibody.
DR Antibodypedia; 3161; 122 antibodies from 22 providers.
DR DNASU; 3742; -.
DR Ensembl; ENST00000280684.3; ENSP00000280684.3; ENSG00000151079.7.
DR GeneID; 3742; -.
DR KEGG; hsa:3742; -.
DR MANE-Select; ENST00000280684.4; ENSP00000280684.3; NM_002235.5; NP_002226.1.
DR UCSC; uc001qng.4; human.
DR CTD; 3742; -.
DR DisGeNET; 3742; -.
DR GeneCards; KCNA6; -.
DR HGNC; HGNC:6225; KCNA6.
DR HPA; ENSG00000151079; Tissue enriched (brain).
DR MIM; 176257; gene.
DR neXtProt; NX_P17658; -.
DR OpenTargets; ENSG00000151079; -.
DR PharmGKB; PA30022; -.
DR VEuPathDB; HostDB:ENSG00000151079; -.
DR eggNOG; KOG1545; Eukaryota.
DR GeneTree; ENSGT00940000162469; -.
DR HOGENOM; CLU_011722_4_0_1; -.
DR InParanoid; P17658; -.
DR OMA; MRAEEPL; -.
DR OrthoDB; 695337at2759; -.
DR PhylomeDB; P17658; -.
DR TreeFam; TF313103; -.
DR PathwayCommons; P17658; -.
DR Reactome; R-HSA-1296072; Voltage gated Potassium channels.
DR SignaLink; P17658; -.
DR BioGRID-ORCS; 3742; 13 hits in 1061 CRISPR screens.
DR ChiTaRS; KCNA6; human.
DR GeneWiki; KCNA6; -.
DR GenomeRNAi; 3742; -.
DR Pharos; P17658; Tclin.
DR PRO; PR:P17658; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; P17658; protein.
DR Bgee; ENSG00000151079; Expressed in cortical plate and 75 other tissues.
DR Genevisible; P17658; HS.
DR GO; GO:0043679; C:axon terminus; IEA:Ensembl.
DR GO; GO:0016021; C:integral component of membrane; IBA:GO_Central.
DR GO; GO:0005887; C:integral component of plasma membrane; IMP:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0034705; C:potassium channel complex; ISS:UniProtKB.
DR GO; GO:0008076; C:voltage-gated potassium channel complex; ISS:UniProtKB.
DR GO; GO:0005251; F:delayed rectifier potassium channel activity; IDA:UniProtKB.
DR GO; GO:0005249; F:voltage-gated potassium channel activity; IBA:GO_Central.
DR GO; GO:0071805; P:potassium ion transmembrane transport; IDA:UniProtKB.
DR GO; GO:0006813; P:potassium ion transport; TAS:ProtInc.
DR GO; GO:0051260; P:protein homooligomerization; IEA:InterPro.
DR GO; GO:0034765; P:regulation of ion transmembrane transport; IEA:UniProtKB-KW.
DR Gene3D; 1.20.120.350; -; 1.
DR Gene3D; 3.30.710.10; -; 1.
DR InterPro; IPR000210; BTB/POZ_dom.
DR InterPro; IPR005821; Ion_trans_dom.
DR InterPro; IPR003968; K_chnl_volt-dep_Kv.
DR InterPro; IPR003972; K_chnl_volt-dep_Kv1.
DR InterPro; IPR004053; KCNA6.
DR InterPro; IPR011333; SKP1/BTB/POZ_sf.
DR InterPro; IPR003131; T1-type_BTB.
DR InterPro; IPR028325; VG_K_chnl.
DR InterPro; IPR027359; Volt_channel_dom_sf.
DR PANTHER; PTHR11537; PTHR11537; 1.
DR PANTHER; PTHR11537:SF104; PTHR11537:SF104; 1.
DR Pfam; PF02214; BTB_2; 1.
DR Pfam; PF00520; Ion_trans; 1.
DR PRINTS; PR01513; KV16CHANNEL.
DR PRINTS; PR01491; KVCHANNEL.
DR PRINTS; PR01496; SHAKERCHANEL.
DR SMART; SM00225; BTB; 1.
DR SUPFAM; SSF54695; SSF54695; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Ion channel; Ion transport; Lipoprotein; Membrane;
KW Palmitate; Phosphoprotein; Potassium; Potassium channel;
KW Potassium transport; Reference proteome; Transmembrane;
KW Transmembrane helix; Transport; Voltage-gated channel.
FT CHAIN 1..529
FT /note="Potassium voltage-gated channel subfamily A member
FT 6"
FT /id="PRO_0000053990"
FT TOPO_DOM 1..171
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TRANSMEM 172..193
FT /note="Helical; Name=Segment S1"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TOPO_DOM 194..262
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TRANSMEM 263..284
FT /note="Helical; Name=Segment S2"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TOPO_DOM 285..295
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TRANSMEM 296..316
FT /note="Helical; Name=Segment S3"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TOPO_DOM 317..337
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TRANSMEM 338..358
FT /note="Helical; Voltage-sensor; Name=Segment S4"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TOPO_DOM 359..373
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TRANSMEM 374..395
FT /note="Helical; Name=Segment S5"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TOPO_DOM 396..409
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT INTRAMEM 410..421
FT /note="Helical; Name=Pore helix"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT INTRAMEM 422..429
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TOPO_DOM 430..436
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TRANSMEM 437..465
FT /note="Helical; Name=Segment S6"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TOPO_DOM 466..529
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT REGION 1..33
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 210..233
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 360..373
FT /note="S4-S5 linker"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT REGION 488..513
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 422..427
FT /note="Selectivity filter"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT MOTIF 527..529
FT /note="PDZ-binding"
FT /evidence="ECO:0000255"
FT MOD_RES 3
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q61923"
FT MOD_RES 511
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000305"
FT LIPID 285
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 529 AA; 58729 MW; CFF0710A1F9CD69F CRC64;
MRSEKSLTLA APGEVRGPEG EQQDAGDFPE AGGGGGCCSS ERLVINISGL RFETQLRTLS
LFPDTLLGDP GRRVRFFDPL RNEYFFDRNR PSFDAILYYY QSGGRLRRPV NVPLDIFLEE
IRFYQLGDEA LAAFREDEGC LPEGGEDEKP LPSQPFQRQV WLLFEYPESS GPARGIAIVS
VLVILISIVI FCLETLPQFR VDGRGGNNGG VSRVSPVSRG SQEEEEDEDD SYTFHHGITP
GEMGTGGSSS LSTLGGSFFT DPFFLVETLC IVWFTFELLV RFSACPSKPA FFRNIMNIID
LVAIFPYFIT LGTELVQQQE QQPASGGGGQ NGQQAMSLAI LRVIRLVRVF RIFKLSRHSK
GLQILGKTLQ ASMRELGLLI FFLFIGVILF SSAVYFAEAD DDDSLFPSIP DAFWWAVVTM
TTVGYGDMYP MTVGGKIVGS LCAIAGVLTI ALPVPVIVSN FNYFYHRETE QEEQGQYTHV
TCGQPAPDLR ATDNGLGKPD FPEANRERRP SYLPTPHRAY AEKRMLTEV
