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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

  1. potassium channel activity Source: ProtInc
  2. voltage-gated ion channel activity Source: UniProtKB-KW

GO - Biological processi

  1. potassium ion transport Source: ProtInc
  2. 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_75819. TWIK related potassium channel (TREK).

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
ProteomesiUP000005640 Componenti: Chromosome 11

Organism-specific databases

HGNCiHGNC:6279. KCNK4.

Subcellular locationi

Cell membrane 4 Publications; Multi-pass membrane protein 4 Publications

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 33Cytoplasmic4 Publications
Transmembranei4 – 2421Helical4 PublicationsAdd
BLAST
Topological domaini25 – 8763Extracellular4 PublicationsAdd
BLAST
Intramembranei88 – 10215Helical; Name=Pore helix 14 PublicationsAdd
BLAST
Intramembranei103 – 10974 Publications
Topological domaini110 – 1178Extracellular4 Publications
Transmembranei118 – 15033Helical4 PublicationsAdd
BLAST
Topological domaini151 – 17222Cytoplasmic4 PublicationsAdd
BLAST
Transmembranei173 – 19422Helical4 PublicationsAdd
BLAST
Topological domaini195 – 1995Extracellular4 Publications
Intramembranei200 – 21314Helical; Name=Pore helix 24 PublicationsAdd
BLAST
Intramembranei214 – 21964 Publications
Topological domaini220 – 23314Extracellular4 PublicationsAdd
BLAST
Transmembranei234 – 26027Helical4 PublicationsAdd
BLAST
Topological domaini261 – 393133Cytoplasmic4 PublicationsAdd
BLAST

GO - Cellular componenti

  1. integral component of membrane Source: UniProtKB-KW
  2. plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi98 – 981G → I: Strongly increases basal level of channel activity, decreases further activation by pressure and abolishes further activation by arachidonic acid. 1 Publication
Mutagenesisi236 – 2361W → S: Increases basal level of channel activity and decreases further activation by pressure, but has little effect on further activation by arachidonic acid. 1 Publication

Organism-specific databases

PharmGKBiPA30061.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 393393Potassium channel subfamily K member 4PRO_0000101747Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi52 – 52Interchain4 Publications
Glycosylationi78 – 781N-linked (GlcNAc...)Sequence Analysis
Glycosylationi82 – 821N-linked (GlcNAc...)Sequence Analysis

Post-translational modificationi

N-glycosylated.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ9NYG8.
PRIDEiQ9NYG8.

PTM databases

PhosphoSiteiQ9NYG8.

Expressioni

Gene expression databases

BgeeiQ9NYG8.
CleanExiHS_KCNK4.
ExpressionAtlasiQ9NYG8. baseline.
GenevestigatoriQ9NYG8.

Interactioni

Subunit structurei

Homodimer; disulfide-linked.4 Publications

Protein-protein interaction databases

BioGridi119122. 2 interactions.
IntActiQ9NYG8. 2 interactions.
STRINGi9606.ENSP00000378033.

Structurei

Secondary structure

1
393
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi3 – 2826Combined sources
Helixi29 – 313Combined sources
Helixi34 – 4916Combined sources
Helixi55 – 7016Combined sources
Beta strandi87 – 893Combined sources
Helixi90 – 10112Combined sources
Helixi114 – 15946Combined sources
Helixi164 – 18320Combined sources
Helixi185 – 19511Combined sources
Helixi199 – 21012Combined sources
Beta strandi216 – 2183Combined sources
Beta strandi221 – 2233Combined sources
Helixi231 – 25929Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
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. Positions 2-260.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni103 – 1086Selectivity filter 14 Publications
Regioni212 – 2176Selectivity filter 24 Publications

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

eggNOGiNOG280717.
GeneTreeiENSGT00760000118858.
HOGENOMiHOG000013106.
HOVERGENiHBG052234.
InParanoidiQ9NYG8.
KOiK04915.
OMAiAYQPLVW.
PhylomeDBiQ9NYG8.
TreeFamiTF313947.

Family and domain databases

InterProiIPR003280. 2pore_dom_K_chnl.
IPR013099. 2pore_dom_K_chnl_dom.
IPR008074. 2pore_dom_K_chnl_TRAAK.
[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 20, 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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti328 – 3281P → L.1 Publication
Corresponds to variant rs953778 [ dbSNP | Ensembl ].
VAR_020206

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 11M → MTTAPQEPPARPLQAGSGAG PAPGRAM in isoform 2. 1 PublicationVSP_006689

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_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.1. human. [Q9NYG8-1]

Polymorphism databases

DMDMi13124080.

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_201567.1. NM_033310.2. [Q9NYG8-1]
UniGeneiHs.647233.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
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. Positions 2-260.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi119122. 2 interactions.
IntActiQ9NYG8. 2 interactions.
STRINGi9606.ENSP00000378033.

Chemistry

GuidetoPHARMACOLOGYi516.

PTM databases

PhosphoSiteiQ9NYG8.

Polymorphism databases

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.1. human. [Q9NYG8-1]

Organism-specific databases

CTDi50801.
GeneCardsiGC11P064058.
HGNCiHGNC:6279. KCNK4.
MIMi605720. gene.
neXtProtiNX_Q9NYG8.
PharmGKBiPA30061.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG280717.
GeneTreeiENSGT00760000118858.
HOGENOMiHOG000013106.
HOVERGENiHBG052234.
InParanoidiQ9NYG8.
KOiK04915.
OMAiAYQPLVW.
PhylomeDBiQ9NYG8.
TreeFamiTF313947.

Enzyme and pathway databases

ReactomeiREACT_75819. TWIK related potassium channel (TREK).

Miscellaneous databases

GeneWikiiKCNK4.
GenomeRNAii50801.
NextBioi53228.
PROiQ9NYG8.
SOURCEiSearch...

Gene expression databases

BgeeiQ9NYG8.
CleanExiHS_KCNK4.
ExpressionAtlasiQ9NYG8. baseline.
GenevestigatoriQ9NYG8.

Family and domain databases

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

Publicationsi

« Hide 'large scale' publications
  1. "Cloning, localisation and functional expression of a novel human, cerebellum specific, two pore domain potassium channel."
    Chapman C.G., Meadows H.J., Godden R.J., Campbell D.A., Duckworth M., Kelsell R.E., Murdock P.R., Randall A.D., Rennie G.I., Gloger I.S.
    Brain Res. Mol. Brain Res. 82:74-83(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    Tissue: Brain.
  2. "Assignment of KCNK4 encoding the human potassium channel TRAAK to chromosome 11."
    Gray A.T.
    Submitted (FEB-2000) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT LEU-328.
    Tissue: Frontal cortex.
  3. "Cloning and expression of human TRAAK, a polyunsaturated fatty acids-activated and mechano-sensitive K(+) channel."
    Lesage F., Maingret F., Lazdunski M.
    FEBS Lett. 471:137-140(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
  4. "Cloning of two transcripts, HKT4.1a and HKT4.1b, from the human two-pore K+ channel gene KCNK4. Chromosomal localization, tissue distribution and functional expression."
    Ozaita A., Vega-Saenz de Miera E.
    Brain Res. Mol. Brain Res. 102:18-27(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
  5. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] (ISOFORM 1).
  6. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  7. Cited for: SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S).
  8. "Crystal structure of the human K2P TRAAK, a lipid- and mechano-sensitive K+ ion channel."
    Brohawn S.G., del Marmol J., MacKinnon R.
    Science 335:436-441(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (3.31 ANGSTROMS) OF 1-274, FUNCTION, ENZYME REGULATION, SUBUNIT, SUBCELLULAR LOCATION, TOPOLOGY, GLYCOSYLATION, DISULFIDE BOND.
  9. "Domain-swapped chain connectivity and gated membrane access in a Fab-mediated crystal of the human TRAAK K+ channel."
    Brohawn S.G., Campbell E.B., MacKinnon R.
    Proc. Natl. Acad. Sci. U.S.A. 110:2129-2134(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.75 ANGSTROMS) OF 1-274, SUBCELLULAR LOCATION, SUBUNIT, TOPOLOGY, DISULFIDE BOND.
  10. "Physical mechanism for gating and mechanosensitivity of the human TRAAK K+ channel."
    Brohawn S.G., Campbell E.B., MacKinnon R.
    Nature 516:126-130(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 1-264, FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, TOPOLOGY, DISULFIDE BOND, DOMAIN.
  11. "Transmembrane helix straightening and buckling underlies activation of mechanosensitive and thermosensitive K(2P) channels."
    Lolicato M., Riegelhaupt P.M., Arrigoni C., Clark K.A., Minor D.L. Jr.
    Neuron 84:1198-1212(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (3.30 ANGSTROMS) OF 1-274 OF MUTANTS ILE-98 AND SER-236, FUNCTION, ENZYME REGULATION, SUBCELLULAR LOCATION, SUBUNIT, TOPOLOGY, DISULFIDE BOND, DOMAIN, MUTAGENESIS OF GLY-98 AND TRP-236.

Entry informationi

Entry nameiKCNK4_HUMAN
AccessioniPrimary (citable) accession number: Q9NYG8
Secondary accession number(s): B5TJL1, Q96T94
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 20, 2001
Last sequence update: February 20, 2001
Last modified: March 31, 2015
This is version 128 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

External Data

Dasty 3

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 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.