KCNA4_RAT
ID KCNA4_RAT Reviewed; 655 AA.
AC P15385;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1990, sequence version 1.
DT 25-MAY-2022, entry version 184.
DE RecName: Full=Potassium voltage-gated channel subfamily A member 4;
DE AltName: Full=RCK4 {ECO:0000303|PubMed:2348860};
DE AltName: Full=RHK1;
DE AltName: Full=RK3;
DE AltName: Full=Voltage-gated potassium channel subunit Kv1.4;
GN Name=Kcna4;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RX PubMed=2555158; DOI=10.1002/j.1460-2075.1989.tb08483.x;
RA Stuehmer W., Ruppersberg J.P., Schroerter K.H., Sakmann B., Stocker M.,
RA Giese K.P., Perschke A., Baumann A., Pongs O.;
RT "Molecular basis of functional diversity of voltage-gated potassium
RT channels in mammalian brain.";
RL EMBO J. 8:3235-3244(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND SUBCELLULAR LOCATION.
RC STRAIN=Sprague-Dawley; TISSUE=Heart;
RX PubMed=2384173; DOI=10.1016/0014-5793(90)80973-m;
RA Tseng-Crank J., Tseng G.-N., Schwartz A., Tanouye M.A.;
RT "Molecular cloning and functional expression of a potassium channel cDNA
RT isolated from a rat cardiac library.";
RL FEBS Lett. 268:63-68(1990).
RN [3]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH KCNA1.
RX PubMed=2348860; DOI=10.1038/345535a0;
RA Ruppersberg J.P., Schroeter K.H., Sakmann B., Stocker M., Sewing S.,
RA Pongs O.;
RT "Heteromultimeric channels formed by rat brain potassium-channel
RT proteins.";
RL Nature 345:535-537(1990).
RN [4]
RP SUBCELLULAR LOCATION.
RX PubMed=1497894; DOI=10.1016/0896-6273(92)90166-b;
RA Sheng M., Tsaur M.L., Jan Y.N., Jan L.Y.;
RT "Subcellular segregation of two A-type K+ channel proteins in rat central
RT neurons.";
RL Neuron 9:271-284(1992).
RN [5]
RP FUNCTION.
RX PubMed=8495559; DOI=10.1161/01.res.72.6.1326;
RA Po S., Roberds S., Snyders D.J., Tamkun M.M., Bennett P.B.;
RT "Heteromultimeric assembly of human potassium channels. Molecular basis of
RT a transient outward current?";
RL Circ. Res. 72:1326-1336(1993).
RN [6]
RP INTERACTION WITH KCNA2, FUNCTION, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=8361540; DOI=10.1038/365072a0;
RA Sheng M., Liao Y.J., Jan Y.N., Jan L.Y.;
RT "Presynaptic A-current based on heteromultimeric K+ channels detected in
RT vivo.";
RL Nature 365:72-75(1993).
RN [7]
RP INTERACTION WITH DLG1; DLG2 AND DLG4.
RX PubMed=7477295; DOI=10.1038/378085a0;
RA Kim E., Niethammer M., Rothschild A., Jan Y.N., Sheng M.;
RT "Clustering of Shaker-type K+ channels by interaction with a family of
RT membrane-associated guanylate kinases.";
RL Nature 378:85-88(1995).
RN [8]
RP INTERACTION WITH KCNAB1 AND KCNAB2, AND TISSUE SPECIFICITY.
RX PubMed=9334400; DOI=10.1523/jneurosci.17-21-08246.1997;
RA Rhodes K.J., Strassle B.W., Monaghan M.M., Bekele-Arcuri Z., Matos M.F.,
RA Trimmer J.S.;
RT "Association and colocalization of the Kvbeta1 and Kvbeta2 beta-subunits
RT with Kv1 alpha-subunits in mammalian brain K+ channel complexes.";
RL J. Neurosci. 17:8246-8258(1997).
RN [9]
RP INTERACTION WITH KCNA1 AND KCNA2, SUBCELLULAR LOCATION, AND GLYCOSYLATION.
RX PubMed=10896669; DOI=10.1074/jbc.m005010200;
RA Manganas L.N., Trimmer J.S.;
RT "Subunit composition determines Kv1 potassium channel surface expression.";
RL J. Biol. Chem. 275:29685-29693(2000).
RN [10]
RP INTERACTION WITH SIGMAR1.
RX PubMed=11988171; DOI=10.1016/s0896-6273(02)00677-3;
RA Aydar E., Palmer C.P., Klyachko V.A., Jackson M.B.;
RT "The sigma receptor as a ligand-regulated auxiliary potassium channel
RT subunit.";
RL Neuron 34:399-410(2002).
RN [11]
RP SUBUNIT, AND INTERACTION WITH KCNA2.
RX PubMed=12632190; DOI=10.1007/s00424-002-0994-7;
RA Fergus D.J., Martens J.R., England S.K.;
RT "Kv channel subunits that contribute to voltage-gated K+ current in renal
RT vascular smooth muscle.";
RL Pflugers Arch. 445:697-704(2003).
RN [12]
RP INTERACTION WITH LGI1; KCNA1 AND KCNAB1.
RX PubMed=16504945; DOI=10.1016/j.neuron.2006.01.033;
RA Schulte U., Thumfart J.-O., Kloecker N., Sailer C.A., Bildl W.,
RA Biniossek M., Dehn D., Deller T., Eble S., Abbass K., Wangler T.,
RA Knaus H.-G., Fakler B.;
RT "The epilepsy-linked Lgi1 protein assembles into presynaptic Kv1 channels
RT and inhibits inactivation by Kvbeta1.";
RL Neuron 49:697-706(2006).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-123, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
RN [14]
RP STRUCTURE BY NMR OF 1-37.
RX PubMed=9000078; DOI=10.1038/385272a0;
RA Antz C., Geyer M., Fakler B., Schott M.K., Guy H.R., Frank R.,
RA Ruppersberg J.P., Kalbitzer H.R.;
RT "NMR structure of inactivation gates from mammalian voltage-dependent
RT potassium channels.";
RL Nature 385:272-275(1997).
RN [15]
RP STRUCTURE BY NMR OF 25-75.
RX PubMed=12590144; DOI=10.1074/jbc.m210191200;
RA Wissmann R., Bildl W., Oliver D., Beyermann M., Kalbitzer H.-R.,
RA Bentrop D., Fakler B.;
RT "Solution structure and function of the 'tandem inactivation domain' of the
RT neuronal A-type potassium channel Kv1.4.";
RL J. Biol. Chem. 278:16142-16150(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. The channel alternates between opened
CC and closed conformations in response to the voltage difference across
CC the membrane. Can form functional homotetrameric channels and
CC heterotetrameric channels that contain variable proportions of KCNA1,
CC KCNA2, KCNA4, KCNA5, and possibly other family members as well; channel
CC properties depend on the type of alpha subunits that are part of the
CC channel (PubMed:2348860, PubMed:8495559, PubMed:10896669). Channel
CC properties are modulated by cytoplasmic beta subunits that regulate the
CC subcellular location of the alpha subunits and promote rapid
CC inactivation. In vivo, membranes probably contain a mixture of
CC heteromeric potassium channel complexes, making it difficult to assign
CC currents observed in intact tissues to any particular potassium channel
CC family member. Homotetrameric KCNA4 forms a potassium channel that
CC opens in response to membrane depolarization, followed by rapid
CC spontaneous channel closure (PubMed:2384173). Likewise, a
CC heterotetrameric channel formed by KCNA1 and KCNA4 shows rapid
CC inactivation (PubMed:2348860). {ECO:0000269|PubMed:10896669,
CC ECO:0000269|PubMed:2348860, ECO:0000269|PubMed:2384173,
CC ECO:0000269|PubMed:8495559}.
CC -!- SUBUNIT: Homotetramer and heterotetramer of potassium channel proteins
CC (PubMed:10896669). Interacts with KCNAB1 and KCNAB2 (PubMed:9334400).
CC Binds PDZ domains of DLG1, DLG2 and DLG4. Interacts with SIGMAR1
CC (PubMed:11988171). Part of a complex containing KCNA1, KCNAB1 and LGI1
CC (PubMed:16504945). Detected in a complex with KCNA1 (PubMed:2348860,
CC PubMed:10896669). Interacts with KCNA2 (PubMed:8361540,
CC PubMed:10896669, PubMed:12632190). Interacts (via cytoplasmic N-
CC terminal domain) with KCNRG (By similarity).
CC {ECO:0000250|UniProtKB:P22459, ECO:0000269|PubMed:10896669,
CC ECO:0000269|PubMed:11988171, ECO:0000269|PubMed:12632190,
CC ECO:0000269|PubMed:16504945, ECO:0000269|PubMed:2348860,
CC ECO:0000269|PubMed:7477295, ECO:0000269|PubMed:8361540,
CC ECO:0000269|PubMed:9334400}.
CC -!- INTERACTION:
CC P15385; P78352: DLG4; Xeno; NbExp=9; IntAct=EBI-631417, EBI-80389;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:10896669,
CC ECO:0000269|PubMed:2348860, ECO:0000269|PubMed:2384173}; Multi-pass
CC membrane protein {ECO:0000255}. Cell projection, axon
CC {ECO:0000269|PubMed:10896669, ECO:0000269|PubMed:1497894,
CC ECO:0000305|PubMed:8361540}.
CC -!- TISSUE SPECIFICITY: Detected in brain (at protein level)
CC (PubMed:8361540, PubMed:9334400). Heart and brain.
CC {ECO:0000269|PubMed:2384173, ECO:0000269|PubMed:8361540,
CC ECO:0000269|PubMed:9334400}.
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. {ECO:0000305}.
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 -!- PTM: N-glycosylated. {ECO:0000269|PubMed:10896669}.
CC -!- SIMILARITY: Belongs to the potassium channel family. A (Shaker) (TC
CC 1.A.1.2) subfamily. Kv1.4/KCNA4 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; X16002; CAA34133.1; -; mRNA.
DR EMBL; M32867; AAA41469.1; -; mRNA.
DR PIR; S11049; S11049.
DR RefSeq; NP_037103.1; NM_012971.2.
DR PDB; 1KN7; NMR; -; A=1-75.
DR PDB; 1ZTO; NMR; -; A=1-36.
DR PDBsum; 1KN7; -.
DR PDBsum; 1ZTO; -.
DR AlphaFoldDB; P15385; -.
DR BMRB; P15385; -.
DR SMR; P15385; -.
DR BioGRID; 247502; 2.
DR CORUM; P15385; -.
DR IntAct; P15385; 5.
DR MINT; P15385; -.
DR STRING; 10116.ENSRNOP00000006524; -.
DR BindingDB; P15385; -.
DR ChEMBL; CHEMBL5583; -.
DR DrugCentral; P15385; -.
DR GuidetoPHARMACOLOGY; 541; -.
DR GlyGen; P15385; 1 site.
DR iPTMnet; P15385; -.
DR PhosphoSitePlus; P15385; -.
DR PaxDb; P15385; -.
DR ABCD; P15385; 2 sequenced antibodies.
DR GeneID; 25469; -.
DR KEGG; rno:25469; -.
DR UCSC; RGD:2952; rat.
DR CTD; 3739; -.
DR RGD; 2952; Kcna4.
DR eggNOG; KOG1545; Eukaryota.
DR InParanoid; P15385; -.
DR PhylomeDB; P15385; -.
DR Reactome; R-RNO-1296072; Voltage gated Potassium channels.
DR EvolutionaryTrace; P15385; -.
DR PRO; PR:P15385; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0032279; C:asymmetric synapse; IDA:SynGO-UCL.
DR GO; GO:0030424; C:axon; IDA:UniProtKB.
DR GO; GO:0043194; C:axon initial segment; ISO:RGD.
DR GO; GO:0009986; C:cell surface; IDA:RGD.
DR GO; GO:0043198; C:dendritic shaft; IDA:SynGO-UCL.
DR GO; GO:0043197; C:dendritic spine; IDA:SynGO-UCL.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:RGD.
DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR GO; GO:0016021; C:integral component of membrane; IDA:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:RGD.
DR GO; GO:0099055; C:integral component of postsynaptic membrane; IDA:SynGO-UCL.
DR GO; GO:0099056; C:integral component of presynaptic membrane; IDA:SynGO-UCL.
DR GO; GO:0016020; C:membrane; ISO:RGD.
DR GO; GO:0008076; C:voltage-gated potassium channel complex; IDA:UniProtKB.
DR GO; GO:0005251; F:delayed rectifier potassium channel activity; IBA:GO_Central.
DR GO; GO:0005216; F:ion channel activity; IDA:RGD.
DR GO; GO:0005267; F:potassium channel activity; IDA:RGD.
DR GO; GO:0030955; F:potassium ion binding; IEA:InterPro.
DR GO; GO:0005249; F:voltage-gated potassium channel activity; IDA:RGD.
DR GO; GO:0071805; P:potassium ion transmembrane transport; IMP:UniProtKB.
DR GO; GO:0006813; P:potassium ion transport; TAS:RGD.
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; 1.20.5.600; -; 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; IPR020467; K_chnl_volt-dep_Kv1.4.
DR InterPro; IPR012897; K_chnl_volt-dep_Kv1.4_TID.
DR InterPro; IPR037065; K_chnl_volt-dep_Kv1.4_TID_sf.
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 Pfam; PF02214; BTB_2; 1.
DR Pfam; PF00520; Ion_trans; 1.
DR Pfam; PF07941; K_channel_TID; 1.
DR PRINTS; PR01511; KV14CHANNEL.
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 3D-structure; Cell membrane; Cell projection; Glycoprotein; Ion channel;
KW Ion transport; Membrane; Phosphoprotein; Potassium; Potassium channel;
KW Potassium transport; Reference proteome; Transmembrane;
KW Transmembrane helix; Transport; Voltage-gated channel.
FT CHAIN 1..655
FT /note="Potassium voltage-gated channel subfamily A member
FT 4"
FT /id="PRO_0000053984"
FT TOPO_DOM 1..306
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TRANSMEM 307..328
FT /note="Helical; Name=Segment S1"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TOPO_DOM 329..372
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TRANSMEM 373..394
FT /note="Helical; Name=Segment S2"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TOPO_DOM 395..405
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TRANSMEM 406..426
FT /note="Helical; Name=Segment S3"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TOPO_DOM 427..441
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TRANSMEM 442..462
FT /note="Helical; Voltage-sensor; Name=Segment S4"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TOPO_DOM 463..477
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TRANSMEM 478..499
FT /note="Helical; Name=Segment S5"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TOPO_DOM 500..513
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT INTRAMEM 514..525
FT /note="Helical; Name=Pore helix"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT INTRAMEM 526..533
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TOPO_DOM 534..540
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TRANSMEM 541..569
FT /note="Helical; Name=Segment S6"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT TOPO_DOM 570..655
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT REGION 24..153
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 464..477
FT /note="S4-S5 linker"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT REGION 631..655
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 526..531
FT /note="Selectivity filter"
FT /evidence="ECO:0000250|UniProtKB:P63142"
FT MOTIF 653..655
FT /note="PDZ-binding"
FT COMPBIAS 78..92
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 121..141
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 123
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 601
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000255"
FT CARBOHYD 354
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CONFLICT 42
FT /note="A -> L (in Ref. 2; AAA41469)"
FT /evidence="ECO:0000305"
FT CONFLICT 84..88
FT /note="EEEAT -> RRRRQ (in Ref. 2; AAA41469)"
FT /evidence="ECO:0000305"
FT CONFLICT 95
FT /note="Missing (in Ref. 2; AAA41469)"
FT /evidence="ECO:0000305"
FT CONFLICT 310
FT /note="G -> A (in Ref. 2; AAA41469)"
FT /evidence="ECO:0000305"
FT TURN 11..13
FT /evidence="ECO:0007829|PDB:1KN7"
FT HELIX 21..24
FT /evidence="ECO:0007829|PDB:1KN7"
FT HELIX 25..30
FT /evidence="ECO:0007829|PDB:1KN7"
FT HELIX 31..33
FT /evidence="ECO:0007829|PDB:1KN7"
FT HELIX 43..46
FT /evidence="ECO:0007829|PDB:1KN7"
SQ SEQUENCE 655 AA; 73390 MW; 40AEF2F901A05F43 CRC64;
MEVAMVSAES SGCNSHMPYG YAAQARARER ERLAHSRAAA AAAVAAATAA VEGTGGSGGG
PHHHHQTRGA YSSHDPQGSR GSREEEATRT EKKKKLHHRQ SSFPHCSDLM PSGSEEKILR
ELSEEEEDEE EEEEEEEEGR FYYSEEDHGD GCSYTDLLPQ DDGGGGGYSS VRYSDCCERV
VINVSGLRFE TQMKTLAQFP ETLLGDPEKR TQYFDPLRNE YFFDRNRPSF DAILYYYQSG
GRLKRPVNVP FDIFTEEVKF YQLGEEALLK FREDEGFVRE EEDRALPENE FKKQIWLLFE
YPESSSPARG IAIVSVLVIL ISIVIFCLET LPEFRDDRDL IMALSAGGHS RLLNDTSAPH
LENSGHTIFN DPFFIVETVC IVWFSFEFVV RCFACPSQAL FFKNIMNIID IVSILPYFIT
LGTDLAQQQG GGNGQQQQAM SFAILRIIRL VRVFRIFKLS RHSKGLQILG HTLRASMREL
GLLIFFLFIG VILFSSAVYF AEADEPTTHF QSIPDAFWWA VVTMTTVGYG DMKPITVGGK
IVGSLCAIAG VLTIALPVPV IVSNFNYFYH RETENEEQTQ LTQNAVSCPY LPSNLLKKFR
SSTSSSLGDK SEYLEMEEGV KESLCGKEEK CQGKGDDSET DKNNCSNAKA VETDV
