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Protein

Potassium voltage-gated channel subfamily A member 4

Gene

KCNA4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes. Forms tetrameric potassium-selective channels through which potassium ions pass in accordance with their electrochemical gradient. The channel alternates between opened and closed conformations in response to the voltage difference across the membrane (PubMed:19912772, PubMed:8495559). Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCNA1, KCNA2, KCNA4, KCNA5, and possibly other family members as well; channel properties depend on the type of alpha subunits that are part of the channel (PubMed:8495559). Channel properties are modulated by cytoplasmic beta subunits that regulate the subcellular location of the alpha subunits and promote rapid inactivation. In vivo, membranes probably contain a mixture of heteromeric potassium channel complexes, making it difficult to assign currents observed in intact tissues to any particular potassium channel family member. Homotetrameric KCNA4 forms a potassium channel that opens in response to membrane depolarization, followed by rapid spontaneous channel closure (PubMed:19912772, PubMed:8495559). Likewise, a heterotetrameric channel formed by KCNA1 and KCNA4 shows rapid inactivation (PubMed:17156368).3 Publications

Enzyme regulationi

Inhibited by 4-aminopyridine (4-AP), but not by tetraethylammonium (TEA) and charybdotoxin (CTX).1 Publication

GO - Molecular functioni

  • potassium ion binding Source: InterPro
  • voltage-gated potassium channel activity Source: UniProtKB

GO - Biological processi

  • potassium ion transmembrane transport Source: UniProtKB
  • potassium ion transport Source: ProtInc
  • protein homooligomerization Source: InterPro
  • regulation of ion transmembrane transport Source: UniProtKB-KW

Keywordsi

Molecular functionIon channel, Potassium channel, Voltage-gated channel
Biological processIon transport, Potassium transport, Transport
LigandPotassium

Enzyme and pathway databases

ReactomeiR-HSA-1296072 Voltage gated Potassium channels

Names & Taxonomyi

Protein namesi
Recommended name:
Potassium voltage-gated channel subfamily A member 4
Alternative name(s):
HPCN2
Voltage-gated K(+) channel HuKII1 Publication
Voltage-gated potassium channel HBK4
Voltage-gated potassium channel HK11 Publication
Voltage-gated potassium channel subunit Kv1.4
Gene namesi
Name:KCNA4
Synonyms:KCNA4L
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

EuPathDBiHostDB:ENSG00000182255.6
HGNCiHGNC:6222 KCNA4
MIMi176266 gene
neXtProtiNX_P22459

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 304CytoplasmicBy similarityAdd BLAST304
Transmembranei305 – 326Helical; Name=Segment S1By similarityAdd BLAST22
Topological domaini327 – 370ExtracellularBy similarityAdd BLAST44
Transmembranei371 – 392Helical; Name=Segment S2By similarityAdd BLAST22
Topological domaini393 – 403CytoplasmicBy similarityAdd BLAST11
Transmembranei404 – 424Helical; Name=Segment S3By similarityAdd BLAST21
Topological domaini425 – 439ExtracellularBy similarityAdd BLAST15
Transmembranei440 – 460Helical; Voltage-sensor; Name=Segment S4By similarityAdd BLAST21
Topological domaini461 – 475CytoplasmicBy similarityAdd BLAST15
Transmembranei476 – 497Helical; Name=Segment S5By similarityAdd BLAST22
Topological domaini498 – 511ExtracellularBy similarityAdd BLAST14
Intramembranei512 – 523Helical; Name=Pore helixBy similarityAdd BLAST12
Intramembranei524 – 531By similarity8
Topological domaini532 – 538ExtracellularBy similarity7
Transmembranei539 – 567Helical; Name=Segment S6By similarityAdd BLAST29
Topological domaini568 – 653CytoplasmicBy similarityAdd BLAST86

Keywords - Cellular componenti

Cell membrane, Cell projection, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi3739
OpenTargetsiENSG00000182255
PharmGKBiPA207

Chemistry databases

ChEMBLiCHEMBL4205
DrugBankiDB02299 Arginineamide
DB06637 Dalfampridine

Polymorphism and mutation databases

BioMutaiKCNA4
DMDMi313104127

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000539811 – 653Potassium voltage-gated channel subfamily A member 4Add BLAST653

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei90Phosphoserine; by PKASequence analysis1
Modified residuei122PhosphoserineBy similarity1
Glycosylationi352N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei599Phosphoserine; by PKASequence analysis1

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiP22459
PeptideAtlasiP22459
PRIDEiP22459

PTM databases

iPTMnetiP22459
PhosphoSitePlusiP22459

Expressioni

Tissue specificityi

Detected in heart ventricle.1 Publication

Gene expression databases

BgeeiENSG00000182255
CleanExiHS_KCNA4
GenevisibleiP22459 HS

Organism-specific databases

HPAiCAB001977
HPA016422

Interactioni

Subunit structurei

Homotetramer and heterotetramer of potassium channel proteins (By similarity). Interacts with KCNAB1 and KCNAB2 (By similarity). Binds PDZ domains of DLG1, DLG2 and DLG4 (By similarity). Interacts with SIGMAR1 (By similarity). Detected in a complex with KCNA1 (By similarity). Interacts with KCNA2 (By similarity). Part of a complex containing KCNA1, KCNAB1 and LGI1 (By similarity). Interacts (via cytoplasmic N-terminal domain) with KCNRG (PubMed:19968958).By similarity

Binary interactionsi

Show more details

Protein-protein interaction databases

BioGridi109942, 18 interactors
IntActiP22459, 7 interactors
MINTiP22459
STRINGi9606.ENSP00000328511

Chemistry databases

BindingDBiP22459

Structurei

3D structure databases

ProteinModelPortaliP22459
SMRiP22459
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni462 – 475S4-S5 linkerBy similarityAdd BLAST14

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi524 – 529Selectivity filterBy similarity6
Motifi651 – 653PDZ-bindingBy similarity3

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi62 – 65Poly-His4
Compositional biasi123 – 137Poly-GluAdd BLAST15
Compositional biasi162 – 165Poly-Gly4
Compositional biasi433 – 436Poly-Gln4

Domaini

The N-terminus may be important in determining the rate of inactivation of the channel while the tail may play a role in modulation of channel activity and/or targeting of the channel to specific subcellular compartments.By similarity
The transmembrane segment S4 functions as voltage-sensor and is characterized by a series of positively charged amino acids at every third position. Channel opening and closing is effected by a conformation change that affects the position and orientation of the voltage-sensor paddle formed by S3 and S4 within the membrane. A transmembrane electric field that is positive inside would push the positively charged S4 segment outwards, thereby opening the pore, while a field that is negative inside would pull the S4 segment inwards and close the pore. Changes in the position and orientation of S4 are then transmitted to the activation gate formed by the inner helix bundle via the S4-S5 linker region.By similarity

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1545 Eukaryota
COG1226 LUCA
GeneTreeiENSGT00760000118846
HOGENOMiHOG000231015
HOVERGENiHBG052230
InParanoidiP22459
KOiK04877
OMAiRQRPEKK
OrthoDBiEOG091G10NU
PhylomeDBiP22459
TreeFamiTF313103

Family and domain databases

Gene3Di1.20.120.350, 1 hit
1.20.5.600, 1 hit
InterProiView protein in InterPro
IPR000210 BTB/POZ_dom
IPR005821 Ion_trans_dom
IPR003968 K_chnl_volt-dep_Kv
IPR003972 K_chnl_volt-dep_Kv1
IPR020467 K_chnl_volt-dep_Kv1.4
IPR012897 K_chnl_volt-dep_Kv1.4_TID
IPR037065 K_chnl_volt-dep_Kv1.4_TID_sf
IPR011333 SKP1/BTB/POZ_sf
IPR003131 T1-type_BTB
IPR028325 VG_K_chnl
IPR027359 Volt_channel_dom_sf
PANTHERiPTHR11537 PTHR11537, 1 hit
PfamiView protein in Pfam
PF02214 BTB_2, 1 hit
PF00520 Ion_trans, 1 hit
PF07941 K_channel_TID, 1 hit
PRINTSiPR00169 KCHANNEL
PR01511 KV14CHANNEL
PR01491 KVCHANNEL
PR01496 SHAKERCHANEL
SMARTiView protein in SMART
SM00225 BTB, 1 hit
SUPFAMiSSF54695 SSF54695, 1 hit

Sequencei

Sequence statusi: Complete.

P22459-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MEVAMVSAES SGCNSHMPYG YAAQARARER ERLAHSRAAA AAAVAAATAA
60 70 80 90 100
VEGSGGSGGG SHHHHQSRGA CTSHDPQSSR GSRRRRRQRS EKKKAHYRQS
110 120 130 140 150
SFPHCSDLMP SGSEEKILRE LSEEEEDEEE EEEEEEEGRF YYSEDDHGDE
160 170 180 190 200
CSYTDLLPQD EGGGGYSSVR YSDCCERVVI NVSGLRFETQ MKTLAQFPET
210 220 230 240 250
LLGDPEKRTQ YFDPLRNEYF FDRNRPSFDA ILYYYQSGGR LKRPVNVPFD
260 270 280 290 300
IFTEEVKFYQ LGEEALLKFR EDEGFVREEE DRALPENEFK KQIWLLFEYP
310 320 330 340 350
ESSSPARGIA IVSVLVILIS IVIFCLETLP EFRDDRDLVM ALSAGGHGGL
360 370 380 390 400
LNDTSAPHLE NSGHTIFNDP FFIVETVCIV WFSFEFVVRC FACPSQALFF
410 420 430 440 450
KNIMNIIDIV SILPYFITLG TDLAQQQGGG NGQQQQAMSF AILRIIRLVR
460 470 480 490 500
VFRIFKLSRH SKGLQILGHT LRASMRELGL LIFFLFIGVI LFSSAVYFAE
510 520 530 540 550
ADEPTTHFQS IPDAFWWAVV TMTTVGYGDM KPITVGGKIV GSLCAIAGVL
560 570 580 590 600
TIALPVPVIV SNFNYFYHRE TENEEQTQLT QNAVSCPYLP SNLLKKFRSS
610 620 630 640 650
TSSSLGDKSE YLEMEEGVKE SLCAKEEKCQ GKGDDSETDK NNCSNAKAVE

TDV
Length:653
Mass (Da):73,257
Last modified:November 30, 2010 - v2
Checksum:i5E511DB704CCA013
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti38A → R in AAA60034 (PubMed:2263489).Curated1
Sequence conflicti42A → R in AAA60034 (PubMed:2263489).Curated1
Sequence conflicti84 – 88RRRRQ → EEEAT in AAA60034 (PubMed:2263489).Curated5
Sequence conflicti304S → D in AAA60034 (PubMed:2263489).Curated1
Sequence conflicti542S → V in AAA60034 (PubMed:2263489).Curated1
Sequence conflicti631G → A in AAA60034 (PubMed:2263489).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M55514 mRNA Translation: AAA60034.1
M60450 mRNA Translation: AAA61275.1
L02751 mRNA Translation: AAA36140.1
AC124657 Genomic DNA No translation available.
CCDSiCCDS41629.1
PIRiA39922
RefSeqiNP_002224.1, NM_002233.3
UniGeneiHs.592002

Genome annotation databases

EnsembliENST00000328224; ENSP00000328511; ENSG00000182255
GeneIDi3739
KEGGihsa:3739
UCSCiuc001msk.4 human

Similar proteinsi

Entry informationi

Entry nameiKCNA4_HUMAN
AccessioniPrimary (citable) accession number: P22459
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1991
Last sequence update: November 30, 2010
Last modified: March 28, 2018
This is version 169 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome
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Main funding by: National Institutes of Health