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P22459

- KCNA4_HUMAN

UniProt

P22459 - KCNA4_HUMAN

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Protein
Potassium voltage-gated channel subfamily A member 4
Gene
KCNA4, KCNA4L
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

Mediates the voltage-dependent potassium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a potassium-selective channel through which potassium ions may pass in accordance with their electrochemical gradient.

GO - Molecular functioni

  1. potassium ion binding Source: InterPro
  2. protein binding Source: UniProtKB
  3. voltage-gated potassium channel activity Source: ProtInc
Complete GO annotation...

GO - Biological processi

  1. potassium ion transport Source: ProtInc
  2. protein homooligomerization Source: InterPro
  3. synaptic transmission Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Ion channel, Potassium channel, Voltage-gated channel

Keywords - Biological processi

Ion transport, Potassium transport, Transport

Keywords - Ligandi

Potassium

Enzyme and pathway databases

ReactomeiREACT_75770. 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 HuKII
Voltage-gated potassium channel HBK4
Voltage-gated potassium channel HK1
Voltage-gated potassium channel subunit Kv1.4
Gene namesi
Name:KCNA4
Synonyms:KCNA4L
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 11

Organism-specific databases

HGNCiHGNC:6222. KCNA4.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei308 – 32619Helical; Name=Segment S1; Reviewed prediction
Add
BLAST
Transmembranei371 – 39222Helical; Name=Segment S2; Reviewed prediction
Add
BLAST
Transmembranei404 – 42421Helical; Name=Segment S3; Reviewed prediction
Add
BLAST
Transmembranei443 – 46119Helical; Voltage-sensor; Name=Segment S4; Reviewed prediction
Add
BLAST
Transmembranei478 – 49720Helical; Name=Segment S5; Reviewed prediction
Add
BLAST
Transmembranei539 – 56123Helical; Name=Segment S6; Reviewed prediction
Add
BLAST

GO - Cellular componenti

  1. plasma membrane Source: Reactome
  2. voltage-gated potassium channel complex Source: ProtInc
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA207.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 653653Potassium voltage-gated channel subfamily A member 4
PRO_0000053981Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei90 – 901Phosphoserine; by PKA Reviewed prediction
Glycosylationi181 – 1811N-linked (GlcNAc...) Reviewed prediction
Glycosylationi352 – 3521N-linked (GlcNAc...) Reviewed prediction
Modified residuei599 – 5991Phosphoserine; by PKA Reviewed prediction

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiP22459.
PRIDEiP22459.

PTM databases

PhosphoSiteiP22459.

Expressioni

Gene expression databases

BgeeiP22459.
CleanExiHS_KCNA4.
GenevestigatoriP22459.

Organism-specific databases

HPAiCAB001977.
HPA016422.

Interactioni

Subunit structurei

Heterotetramer of potassium channel proteins. Binds PDZ domains of DLG1, DLG2 and DLG4. Interacts with SIGMAR1 By similarity. Part of a complex containing KCNA1, KCNAB1 and LGI1 By similarity.

Binary interactionsi

WithEntry#Exp.IntActNotes
Dlg3Q629364EBI-631235,EBI-349596From a different organism.
DLG4P783522EBI-631235,EBI-80389
Dlg4P310163EBI-631235,EBI-375655From a different organism.

Protein-protein interaction databases

BioGridi109942. 16 interactions.
IntActiP22459. 6 interactions.
MINTiMINT-200816.
STRINGi9606.ENSP00000328511.

Structurei

3D structure databases

ProteinModelPortaliP22459.
SMRiP22459. Positions 1-75, 175-571.

Family & Domainsi

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi524 – 5296Selectivity filter By similarity
Motifi651 – 6533PDZ-binding By similarity

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi62 – 654Poly-His
Compositional biasi123 – 13715Poly-Glu
Add
BLAST
Compositional biasi162 – 1654Poly-Gly
Compositional biasi433 – 4364Poly-Gln

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.
The segment S4 is probably the voltage-sensor and is characterized by a series of positively charged amino acids at every third position.

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG1226.
HOGENOMiHOG000231015.
HOVERGENiHBG052230.
InParanoidiP22459.
KOiK04877.
OMAiKKAHHRQ.
OrthoDBiEOG7M0NRD.
PhylomeDBiP22459.
TreeFamiTF313103.

Family and domain databases

Gene3Di1.20.120.350. 1 hit.
1.20.5.600. 1 hit.
3.30.710.10. 1 hit.
InterProiIPR000210. BTB/POZ-like.
IPR011333. BTB/POZ_fold.
IPR027359. Channel_four-helix_dom.
IPR005821. Ion_trans_dom.
IPR003091. K_chnl.
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.
IPR003131. T1-type_BTB.
IPR028325. VG_K_chnl.
[Graphical view]
PANTHERiPTHR11537. PTHR11537. 1 hit.
PfamiPF02214. BTB_2. 1 hit.
PF00520. Ion_trans. 1 hit.
PF07941. K_channel_TID. 1 hit.
[Graphical view]
PRINTSiPR00169. KCHANNEL.
PR01511. KV14CHANNEL.
PR01491. KVCHANNEL.
PR01496. SHAKERCHANEL.
SMARTiSM00225. BTB. 1 hit.
[Graphical view]
SUPFAMiSSF54695. SSF54695. 1 hit.

Sequencei

Sequence statusi: Complete.

P22459-1 [UniParc]FASTAAdd to Basket

« Hide

MEVAMVSAES SGCNSHMPYG YAAQARARER ERLAHSRAAA AAAVAAATAA    50
VEGSGGSGGG SHHHHQSRGA CTSHDPQSSR GSRRRRRQRS EKKKAHYRQS 100
SFPHCSDLMP SGSEEKILRE LSEEEEDEEE EEEEEEEGRF YYSEDDHGDE 150
CSYTDLLPQD EGGGGYSSVR YSDCCERVVI NVSGLRFETQ MKTLAQFPET 200
LLGDPEKRTQ YFDPLRNEYF FDRNRPSFDA ILYYYQSGGR LKRPVNVPFD 250
IFTEEVKFYQ LGEEALLKFR EDEGFVREEE DRALPENEFK KQIWLLFEYP 300
ESSSPARGIA IVSVLVILIS IVIFCLETLP EFRDDRDLVM ALSAGGHGGL 350
LNDTSAPHLE NSGHTIFNDP FFIVETVCIV WFSFEFVVRC FACPSQALFF 400
KNIMNIIDIV SILPYFITLG TDLAQQQGGG NGQQQQAMSF AILRIIRLVR 450
VFRIFKLSRH SKGLQILGHT LRASMRELGL LIFFLFIGVI LFSSAVYFAE 500
ADEPTTHFQS IPDAFWWAVV TMTTVGYGDM KPITVGGKIV GSLCAIAGVL 550
TIALPVPVIV SNFNYFYHRE TENEEQTQLT QNAVSCPYLP SNLLKKFRSS 600
TSSSLGDKSE YLEMEEGVKE SLCAKEEKCQ GKGDDSETDK NNCSNAKAVE 650
TDV 653
Length:653
Mass (Da):73,257
Last modified:November 30, 2010 - v2
Checksum:i5E511DB704CCA013
GO

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti38 – 381A → R in AAA60034. 1 Publication
Sequence conflicti42 – 421A → R in AAA60034. 1 Publication
Sequence conflicti84 – 885RRRRQ → EEEAT in AAA60034. 1 Publication
Sequence conflicti304 – 3041S → D in AAA60034. 1 Publication
Sequence conflicti542 – 5421S → V in AAA60034. 1 Publication
Sequence conflicti631 – 6311G → A in AAA60034. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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.3. human.

Polymorphism databases

DMDMi313104127.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
M55514 mRNA. Translation: AAA60034.1 .
M60450 mRNA. Translation: AAA61275.1 .
L02751 mRNA. Translation: AAA36140.1 .
AC124657 Genomic DNA. No translation available.
CCDSi CCDS41629.1.
PIRi A39922.
RefSeqi NP_002224.1. NM_002233.3.
UniGenei Hs.592002.

3D structure databases

ProteinModelPortali P22459.
SMRi P22459. Positions 1-75, 175-571.
ModBasei Search...

Protein-protein interaction databases

BioGridi 109942. 16 interactions.
IntActi P22459. 6 interactions.
MINTi MINT-200816.
STRINGi 9606.ENSP00000328511.

Chemistry

BindingDBi P22459.
ChEMBLi CHEMBL2362996.
GuidetoPHARMACOLOGYi 541.

PTM databases

PhosphoSitei P22459.

Polymorphism databases

DMDMi 313104127.

Proteomic databases

PaxDbi P22459.
PRIDEi P22459.

Protocols and materials databases

DNASUi 3739.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000328224 ; ENSP00000328511 ; ENSG00000182255 .
GeneIDi 3739.
KEGGi hsa:3739.
UCSCi uc001msk.3. human.

Organism-specific databases

CTDi 3739.
GeneCardsi GC11M030031.
H-InvDB HIX0036152.
HGNCi HGNC:6222. KCNA4.
HPAi CAB001977.
HPA016422.
MIMi 176266. gene.
neXtProti NX_P22459.
PharmGKBi PA207.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG1226.
HOGENOMi HOG000231015.
HOVERGENi HBG052230.
InParanoidi P22459.
KOi K04877.
OMAi KKAHHRQ.
OrthoDBi EOG7M0NRD.
PhylomeDBi P22459.
TreeFami TF313103.

Enzyme and pathway databases

Reactomei REACT_75770. Voltage gated Potassium channels.

Miscellaneous databases

GeneWikii KCNA4.
GenomeRNAii 3739.
NextBioi 14635.
PROi P22459.
SOURCEi Search...

Gene expression databases

Bgeei P22459.
CleanExi HS_KCNA4.
Genevestigatori P22459.

Family and domain databases

Gene3Di 1.20.120.350. 1 hit.
1.20.5.600. 1 hit.
3.30.710.10. 1 hit.
InterProi IPR000210. BTB/POZ-like.
IPR011333. BTB/POZ_fold.
IPR027359. Channel_four-helix_dom.
IPR005821. Ion_trans_dom.
IPR003091. K_chnl.
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.
IPR003131. T1-type_BTB.
IPR028325. VG_K_chnl.
[Graphical view ]
PANTHERi PTHR11537. PTHR11537. 1 hit.
Pfami PF02214. BTB_2. 1 hit.
PF00520. Ion_trans. 1 hit.
PF07941. K_channel_TID. 1 hit.
[Graphical view ]
PRINTSi PR00169. KCHANNEL.
PR01511. KV14CHANNEL.
PR01491. KVCHANNEL.
PR01496. SHAKERCHANEL.
SMARTi SM00225. BTB. 1 hit.
[Graphical view ]
SUPFAMi SSF54695. SSF54695. 1 hit.
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "Sequence of a human fetal skeletal muscle potassium channel cDNA related to RCK4."
    Philipson L.H., Schaefer K., Lamendola J., Bell G.I., Steiner D.F.
    Nucleic Acids Res. 18:7160-7160(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Skeletal muscle.
  2. "Molecular cloning and characterization of two voltage-gated K+ channel cDNAs from human ventricle."
    Tamkun M.M., Knoth K.M., Walbridge J.A., Kroemer H., Roden D.M., Glover D.M.
    FASEB J. 5:331-337(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Heart.
  3. "Human potassium channel genes: molecular cloning and functional expression."
    Ramaswami M., Gautam M., Kamb A., Rudy B., Tanouye M.A., Mathew M.K.
    Mol. Cell. Neurosci. 1:214-223(1990)
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Brain.
  4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  5. "NMR structure of inactivation gates from mammalian voltage-dependent potassium channels."
    Antz C., Geyer M., Fakler B., Schott M.K., Guy H.R., Frank R., Ruppersberg J.P., Kalbitzer H.R.
    Nature 385:272-275(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR OF 1-37.

Entry informationi

Entry nameiKCNA4_HUMAN
AccessioniPrimary (citable) accession number: P22459
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1991
Last sequence update: November 30, 2010
Last modified: September 3, 2014
This is version 138 of the entry and version 2 of the sequence. [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

Documents

  1. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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