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Protein

Potassium channel subfamily K member 4

Gene

KCNK4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Voltage-insensitive potassium channel (PubMed:22282805). Channel opening is triggered by mechanical forces that deform the membrane (PubMed:22282805, PubMed:25471887, PubMed:25500157). Channel opening is triggered by raising the intracellular pH to basic levels (By similarity). The channel is inactive at 24 degrees Celsius (in vitro); raising the temperature to 37 degrees Celsius increases the frequency of channel opening, with a further increase in channel activity when the temperature is raised to 42 degrees Celsius (By similarity). Plays a role in the perception of pain caused by heat (By similarity). Plays a role in the sensory perception of pain caused by pressure (By similarity).By similarity3 Publications

Enzyme regulationi

Activated by arachidonic acid.2 Publications

GO - Molecular functioni

GO - Biological processi

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

BioCyciZFISH:ENSG00000004469-MONOMER.
ReactomeiR-HSA-1299503. TWIK related potassium channel (TREK).
R-HSA-5576886. Phase 4 - resting membrane potential.

Names & Taxonomyi

Protein namesi
Recommended name:
Potassium channel subfamily K member 4
Alternative name(s):
TWIK-related arachidonic acid-stimulated potassium channel protein1 Publication
Short name:
TRAAK1 Publication
Two pore potassium channel KT4.1
Short name:
Two pore K(+) channel KT4.1
Gene namesi
Name:KCNK4
Synonyms:TRAAK
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

HGNCiHGNC:6279. KCNK4.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 3Cytoplasmic4 Publications3
Transmembranei4 – 24Helical4 PublicationsAdd BLAST21
Topological domaini25 – 87Extracellular4 PublicationsAdd BLAST63
Intramembranei88 – 102Helical; Name=Pore helix 14 PublicationsAdd BLAST15
Intramembranei103 – 1094 Publications7
Topological domaini110 – 117Extracellular4 Publications8
Transmembranei118 – 150Helical4 PublicationsAdd BLAST33
Topological domaini151 – 172Cytoplasmic4 PublicationsAdd BLAST22
Transmembranei173 – 194Helical4 PublicationsAdd BLAST22
Topological domaini195 – 199Extracellular4 Publications5
Intramembranei200 – 213Helical; Name=Pore helix 24 PublicationsAdd BLAST14
Intramembranei214 – 2194 Publications6
Topological domaini220 – 233Extracellular4 PublicationsAdd BLAST14
Transmembranei234 – 260Helical4 PublicationsAdd BLAST27
Topological domaini261 – 393Cytoplasmic4 PublicationsAdd BLAST133

GO - Cellular componenti

  • integral component of plasma membrane Source: UniProtKB
  • plasma membrane Source: Reactome
  • potassium channel complex Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi98G → I: Strongly increases basal level of channel activity, decreases further activation by pressure and abolishes further activation by arachidonic acid. 1 Publication1
Mutagenesisi236W → S: Increases basal level of channel activity and decreases further activation by pressure, but has little effect on further activation by arachidonic acid. 1 Publication1

Organism-specific databases

OpenTargetsiENSG00000182450.
PharmGKBiPA30061.

Chemistry databases

GuidetoPHARMACOLOGYi516.

Polymorphism and mutation databases

BioMutaiKCNK4.
DMDMi13124080.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001017471 – 393Potassium channel subfamily K member 4Add BLAST393

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi52Interchain4 Publications
Glycosylationi78N-linked (GlcNAc...)Sequence analysis1
Glycosylationi82N-linked (GlcNAc...)Sequence analysis1

Post-translational modificationi

N-glycosylated.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ9NYG8.
PRIDEiQ9NYG8.

PTM databases

PhosphoSitePlusiQ9NYG8.

Expressioni

Gene expression databases

BgeeiENSG00000182450.
CleanExiHS_KCNK4.
ExpressionAtlasiQ9NYG8. baseline and differential.
GenevisibleiQ9NYG8. HS.

Organism-specific databases

HPAiCAB025086.

Interactioni

Subunit structurei

Homodimer; disulfide-linked.4 Publications

Protein-protein interaction databases

BioGridi119122. 2 interactors.
DIPiDIP-61343N.
IntActiQ9NYG8. 2 interactors.
STRINGi9606.ENSP00000378033.

Structurei

Secondary structure

1393
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi3 – 28Combined sources26
Helixi29 – 31Combined sources3
Helixi34 – 49Combined sources16
Helixi55 – 70Combined sources16
Beta strandi87 – 89Combined sources3
Helixi90 – 101Combined sources12
Helixi114 – 159Combined sources46
Helixi164 – 183Combined sources20
Helixi185 – 195Combined sources11
Helixi199 – 210Combined sources12
Beta strandi216 – 218Combined sources3
Beta strandi221 – 223Combined sources3
Turni225 – 227Combined sources3
Helixi231 – 259Combined sources29

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3UM7X-ray3.31A/B1-274[»]
4I9WX-ray2.75A/B1-274[»]
4RUEX-ray3.30A/B1-274[»]
4RUFX-ray3.40A/B1-274[»]
4WFEX-ray2.50A/B1-264[»]
4WFFX-ray2.50A/B1-264[»]
4WFGX-ray3.00A/B1-264[»]
4WFHX-ray3.01A/B1-264[»]
ProteinModelPortaliQ9NYG8.
SMRiQ9NYG8.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni103 – 108Selectivity filter 14 Publications6
Regioni212 – 217Selectivity filter 24 Publications6

Domaini

Channel opening is brought about by a conformation change that involves buckling of the second transmembrane helix and affects the position and orientation of the fourth transmembrane helix.2 Publications

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1418. Eukaryota.
COG1226. LUCA.
GeneTreeiENSGT00760000118858.
HOGENOMiHOG000013106.
HOVERGENiHBG052234.
InParanoidiQ9NYG8.
KOiK04915.
OMAiLDYPSEN.
OrthoDBiEOG091G0E3R.
PhylomeDBiQ9NYG8.
TreeFamiTF313947.

Family and domain databases

InterProiIPR003280. 2pore_dom_K_chnl.
IPR008074. 2pore_dom_K_chnl_TRAAK.
IPR013099. K_chnl_dom.
[Graphical view]
PfamiPF07885. Ion_trans_2. 2 hits.
[Graphical view]
PRINTSiPR01333. 2POREKCHANEL.
PR01691. TRAAKCHANNEL.

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9NYG8-1) [UniParc]FASTAAdd to basket
Also known as: KT4.1a

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MRSTTLLALL ALVLLYLVSG ALVFRALEQP HEQQAQRELG EVREKFLRAH
60 70 80 90 100
PCVSDQELGL LIKEVADALG GGADPETNST SNSSHSAWDL GSAFFFSGTI
110 120 130 140 150
ITTIGYGNVA LRTDAGRLFC IFYALVGIPL FGILLAGVGD RLGSSLRHGI
160 170 180 190 200
GHIEAIFLKW HVPPELVRVL SAMLFLLIGC LLFVLTPTFV FCYMEDWSKL
210 220 230 240 250
EAIYFVIVTL TTVGFGDYVA GADPRQDSPA YQPLVWFWIL LGLAYFASVL
260 270 280 290 300
TTIGNWLRVV SRRTRAEMGG LTAQAASWTG TVTARVTQRA GPAAPPPEKE
310 320 330 340 350
QPLLPPPPCP AQPLGRPRSP SPPEKAQPPS PPTASALDYP SENLAFIDES
360 370 380 390
SDTQSERGCP LPRAPRGRRR PNPPRKPVRP RGPGRPRDKG VPV
Length:393
Mass (Da):42,704
Last modified:February 21, 2001 - v2
Checksum:i7F18E53A0A9AD57D
GO
Isoform 2 (identifier: Q9NYG8-2) [UniParc]FASTAAdd to basket
Also known as: KT4.1b

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MTTAPQEPPARPLQAGSGAGPAPGRAM

Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
Show »
Length:419
Mass (Da):45,173
Checksum:iE7DEDE17B30C0FBF
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_020206328P → L.1 PublicationCorresponds to variant rs953778dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0066891M → MTTAPQEPPARPLQAGSGAG PAPGRAM in isoform 2. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF248242 mRNA. Translation: AAG31731.1.
AF247042 mRNA. Translation: AAF64062.1.
AF259500 mRNA. Translation: AAK49389.1.
AF259501 mRNA. Translation: AAK49390.1.
EU978935 mRNA. Translation: ACH86094.1.
CH471076 Genomic DNA. Translation: EAW74242.1.
CCDSiCCDS8067.1. [Q9NYG8-1]
RefSeqiNP_001304019.1. NM_001317090.1. [Q9NYG8-1]
NP_201567.1. NM_033310.2. [Q9NYG8-1]
UniGeneiHs.647233.

Genome annotation databases

EnsembliENST00000394525; ENSP00000378033; ENSG00000182450. [Q9NYG8-1]
ENST00000422670; ENSP00000402797; ENSG00000182450. [Q9NYG8-1]
ENST00000539216; ENSP00000444948; ENSG00000182450. [Q9NYG8-1]
GeneIDi50801.
KEGGihsa:50801.
UCSCiuc001nzj.2. human. [Q9NYG8-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF248242 mRNA. Translation: AAG31731.1.
AF247042 mRNA. Translation: AAF64062.1.
AF259500 mRNA. Translation: AAK49389.1.
AF259501 mRNA. Translation: AAK49390.1.
EU978935 mRNA. Translation: ACH86094.1.
CH471076 Genomic DNA. Translation: EAW74242.1.
CCDSiCCDS8067.1. [Q9NYG8-1]
RefSeqiNP_001304019.1. NM_001317090.1. [Q9NYG8-1]
NP_201567.1. NM_033310.2. [Q9NYG8-1]
UniGeneiHs.647233.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3UM7X-ray3.31A/B1-274[»]
4I9WX-ray2.75A/B1-274[»]
4RUEX-ray3.30A/B1-274[»]
4RUFX-ray3.40A/B1-274[»]
4WFEX-ray2.50A/B1-264[»]
4WFFX-ray2.50A/B1-264[»]
4WFGX-ray3.00A/B1-264[»]
4WFHX-ray3.01A/B1-264[»]
ProteinModelPortaliQ9NYG8.
SMRiQ9NYG8.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi119122. 2 interactors.
DIPiDIP-61343N.
IntActiQ9NYG8. 2 interactors.
STRINGi9606.ENSP00000378033.

Chemistry databases

GuidetoPHARMACOLOGYi516.

PTM databases

PhosphoSitePlusiQ9NYG8.

Polymorphism and mutation databases

BioMutaiKCNK4.
DMDMi13124080.

Proteomic databases

PaxDbiQ9NYG8.
PRIDEiQ9NYG8.

Protocols and materials databases

DNASUi50801.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000394525; ENSP00000378033; ENSG00000182450. [Q9NYG8-1]
ENST00000422670; ENSP00000402797; ENSG00000182450. [Q9NYG8-1]
ENST00000539216; ENSP00000444948; ENSG00000182450. [Q9NYG8-1]
GeneIDi50801.
KEGGihsa:50801.
UCSCiuc001nzj.2. human. [Q9NYG8-1]

Organism-specific databases

CTDi50801.
GeneCardsiKCNK4.
HGNCiHGNC:6279. KCNK4.
HPAiCAB025086.
MIMi605720. gene.
neXtProtiNX_Q9NYG8.
OpenTargetsiENSG00000182450.
PharmGKBiPA30061.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1418. Eukaryota.
COG1226. LUCA.
GeneTreeiENSGT00760000118858.
HOGENOMiHOG000013106.
HOVERGENiHBG052234.
InParanoidiQ9NYG8.
KOiK04915.
OMAiLDYPSEN.
OrthoDBiEOG091G0E3R.
PhylomeDBiQ9NYG8.
TreeFamiTF313947.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000004469-MONOMER.
ReactomeiR-HSA-1299503. TWIK related potassium channel (TREK).
R-HSA-5576886. Phase 4 - resting membrane potential.

Miscellaneous databases

GeneWikiiKCNK4.
GenomeRNAii50801.
PROiQ9NYG8.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000182450.
CleanExiHS_KCNK4.
ExpressionAtlasiQ9NYG8. baseline and differential.
GenevisibleiQ9NYG8. HS.

Family and domain databases

InterProiIPR003280. 2pore_dom_K_chnl.
IPR008074. 2pore_dom_K_chnl_TRAAK.
IPR013099. K_chnl_dom.
[Graphical view]
PfamiPF07885. Ion_trans_2. 2 hits.
[Graphical view]
PRINTSiPR01333. 2POREKCHANEL.
PR01691. TRAAKCHANNEL.
ProtoNetiSearch...

Entry informationi

Entry nameiKCNK4_HUMAN
AccessioniPrimary (citable) accession number: Q9NYG8
Secondary accession number(s): B5TJL1, Q96T94
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 21, 2001
Last sequence update: February 21, 2001
Last modified: November 2, 2016
This is version 141 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.