Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Potassium channel subfamily K member 2

Gene

KCNK2

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

Functioni

Ion channel that contributes to passive transmembrane potassium transport (PubMed:23169818). Reversibly converts between a voltage-insensitive potassium leak channel and a voltage-dependent outward rectifying potassium channel in a phosphorylation-dependent manner (PubMed:11319556). In astrocytes, forms mostly heterodimeric potassium channels with KCNK1, with only a minor proportion of functional channels containing homodimeric KCNK2. In astrocytes, the heterodimer formed by KCNK1 and KCNK2 is required for rapid glutamate release in response to activation of G-protein coupled receptors, such as F2R and CNR1 (By similarity).By similarity3 Publications
Isoform 4: Does not display channel activity but reduces the channel activity of isoform 1 and isoform 2 and reduces cell surface expression of isoform 2.By similarity

Miscellaneous

Activated by volatile general anesthetics such as chloroform, halothane and isoflurane.

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionIon channel, Potassium channel
Biological processIon transport, Potassium transport, Transport
LigandPotassium

Enzyme and pathway databases

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 2
Alternative name(s):
Outward rectifying potassium channel protein TREK-1
TREK-1 K(+) channel subunit
Two pore domain potassium channel TREK-1
Two pore potassium channel TPKC1
Gene namesi
Name:KCNK2
Synonyms:TREK, TREK1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000082482.13
HGNCiHGNC:6277 KCNK2
MIMi603219 gene
neXtProtiNX_O95069

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 – 61CytoplasmicSequence analysisAdd BLAST61
Transmembranei62 – 82HelicalSequence analysisAdd BLAST21
Intramembranei144 – 170Pore-forming; Name=Pore-forming 1Sequence analysisAdd BLAST27
Transmembranei172 – 192HelicalSequence analysisAdd BLAST21
Topological domaini193 – 223CytoplasmicSequence analysisAdd BLAST31
Transmembranei224 – 244HelicalSequence analysisAdd BLAST21
Intramembranei253 – 283Pore-forming; Name=Pore-forming 2Sequence analysisAdd BLAST31
Transmembranei288 – 308HelicalSequence analysisAdd BLAST21
Topological domaini309 – 426CytoplasmicSequence analysisAdd BLAST118

Keywords - Cellular componenti

Cell membrane, Endoplasmic reticulum, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi348S → A: Mimics non-phosphorylated state and has no effect on leak channel activity. 1 Publication1
Mutagenesisi348S → D: Phosphomimetic mutant which causes switch to voltage-dependent outward rectifier channel activity. 1 Publication1

Organism-specific databases

DisGeNETi3776
OpenTargetsiENSG00000082482
PharmGKBiPA30059

Chemistry databases

ChEMBLiCHEMBL2321615
DrugBankiDB00204 Dofetilide
DB04855 Dronedarone
GuidetoPHARMACOLOGYi514

Polymorphism and mutation databases

BioMutaiKCNK2

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001017421 – 426Potassium channel subfamily K member 2Add BLAST426

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi108InterchainCombined sources
Glycosylationi110N-linked (GlcNAc...) asparagineSequence analysisCombined sources1
Glycosylationi134N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei348Phosphoserine; by PKA1 Publication1

Post-translational modificationi

Phosphorylation at Ser-348 controls the reversible conversion from a leak channel to a voltage-dependent channel.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiO95069
PeptideAtlasiO95069
PRIDEiO95069
ProteomicsDBi50637
50638 [O95069-2]
50639 [O95069-3]

PTM databases

iPTMnetiO95069
PhosphoSitePlusiO95069

Expressioni

Tissue specificityi

Isoform 4 is detected in kidney, adrenal gland and brain where it is preferentially expressed in the amygdala but not found in thalamus, hypothalamus, hippocampus or substantia nigra.1 Publication

Gene expression databases

BgeeiENSG00000082482 Expressed in 94 organ(s), highest expression level in left adrenal gland
CleanExiHS_KCNK2
ExpressionAtlasiO95069 baseline and differential
GenevisibleiO95069 HS

Interactioni

Subunit structurei

Homodimer; disulfide-linked (Ref. 13). Heterodimer with KCNK1; disulfide-linked (By similarity). Interacts with BVES; the interaction enhances KCNK2 surface expression and is inhibited by cAMP (PubMed:26642364).By similarity2 Publications

Protein-protein interaction databases

STRINGi9606.ENSP00000394033

Chemistry databases

BindingDBiO95069

Structurei

Secondary structure

1426
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliO95069
SMRiO95069
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni354 – 426Required for basal channel activityBy similarityAdd BLAST73
Regioni378 – 426Essential for chloroform and halothane sensitivityBy similarityAdd BLAST49

Domaini

The C-terminal region of isoform 4 mediates its intracellular retention.By similarity

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1418 Eukaryota
COG1226 LUCA
GeneTreeiENSGT00760000118858
HOGENOMiHOG000137657
HOVERGENiHBG055195
InParanoidiO95069
KOiK04913
OMAiTPCKRTL
OrthoDBiEOG091G0E3R
PhylomeDBiO95069
TreeFamiTF313947

Family and domain databases

InterProiView protein in InterPro
IPR003280 2pore_dom_K_chnl
IPR003976 2pore_dom_K_chnl_TREK
IPR013099 K_chnl_dom
PfamiView protein in Pfam
PF07885 Ion_trans_2, 2 hits
PRINTSiPR01333 2POREKCHANEL
PR01499 TREKCHANNEL

Sequences (4+)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 4 described isoforms and 5 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: O95069-1) [UniParc]FASTAAdd to basket
Also known as: TREK-1b

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
MLPSASRERP GYRAGVAAPD LLDPKSAAQN SKPRLSFSTK PTVLASRVES
60 70 80 90 100
DTTINVMKWK TVSTIFLVVV LYLIIGATVF KALEQPHEIS QRTTIVIQKQ
110 120 130 140 150
TFISQHSCVN STELDELIQQ IVAAINAGII PLGNTSNQIS HWDLGSSFFF
160 170 180 190 200
AGTVITTIGF GNISPRTEGG KIFCIIYALL GIPLFGFLLA GVGDQLGTIF
210 220 230 240 250
GKGIAKVEDT FIKWNVSQTK IRIISTIIFI LFGCVLFVAL PAIIFKHIEG
260 270 280 290 300
WSALDAIYFV VITLTTIGFG DYVAGGSDIE YLDFYKPVVW FWILVGLAYF
310 320 330 340 350
AAVLSMIGDW LRVISKKTKE EVGEFRAHAA EWTANVTAEF KETRRRLSVE
360 370 380 390 400
IYDKFQRATS IKRKLSAELA GNHNQELTPC RRTLSVNHLT SERDVLPPLL
410 420
KTESIYLNGL TPHCAGEEIA VIENIK
Length:426
Mass (Da):47,093
Last modified:April 17, 2007 - v2
Checksum:iDB10382B1803DA13
GO
Isoform 2 (identifier: O95069-2) [UniParc]FASTAAdd to basket
Also known as: TREK-1a

The sequence of this isoform differs from the canonical sequence as follows:
     2-16: Missing.

Show »
Length:411
Mass (Da):45,495
Checksum:iFDE40CAB21B42A1C
GO
Isoform 3 (identifier: O95069-3) [UniParc]FASTAAdd to basket
Also known as: TREK-1c

The sequence of this isoform differs from the canonical sequence as follows:
     1-16: MLPSASRERPGYRAGV → MMNPRAKRDFYL

Show »
Length:422
Mass (Da):46,888
Checksum:i1AD4E0B5C1B6CBE7
GO
Isoform 4 (identifier: O95069-4) [UniParc]FASTAAdd to basket
Also known as: TREK-1e

The sequence of this isoform differs from the canonical sequence as follows:
     1-16: MLPSASRERPGYRAGV → MMNPRAKRDFYL
     213-232: KWNVSQTKIRIISTIIFILF → VDPILNIWTSISLSCGSGSL
     233-426: Missing.

Show »
Length:228
Mass (Da):24,682
Checksum:i3BEEDE6F7B5EE839
GO

Computationally mapped potential isoform sequencesi

There are 5 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
Q6ZW95Q6ZW95_HUMAN
Potassium channel subfamily K membe...
KCNK2
152Annotation score:
F8WDE6F8WDE6_HUMAN
Potassium channel subfamily K membe...
KCNK2
217Annotation score:
C9JXY2C9JXY2_HUMAN
Potassium channel subfamily K membe...
KCNK2
124Annotation score:
C9JDK1C9JDK1_HUMAN
Potassium channel subfamily K membe...
KCNK2
118Annotation score:
B4DGU6B4DGU6_HUMAN
cDNA FLJ58876, highly similar to Po...
KCNK2
156Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti309 – 311DWL → RLV in AAD01203 (Ref. 3) Curated3
Sequence conflicti391S → N in AAD47569 (PubMed:10321245).Curated1
Sequence conflicti411T → A in AAD01203 (Ref. 3) Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0244281 – 16MLPSA…YRAGV → MMNPRAKRDFYL in isoform 3 and isoform 4. 1 PublicationAdd BLAST16
Alternative sequenceiVSP_0244292 – 16Missing in isoform 2. 4 PublicationsAdd BLAST15
Alternative sequenceiVSP_047567213 – 232KWNVS…IFILF → VDPILNIWTSISLSCGSGSL in isoform 4. 1 PublicationAdd BLAST20
Alternative sequenceiVSP_047568233 – 426Missing in isoform 4. 1 PublicationAdd BLAST194

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF129399 mRNA Translation: AAD47569.1
AF171068 mRNA Translation: AAF89743.1
AF004711 mRNA Translation: AAD01203.1
AY552980 mRNA Translation: AAT49015.2
AY552981 mRNA Translation: AAT49016.1
EF165334 mRNA Translation: ABM47413.1
EF165335 mRNA Translation: ABM47414.1
AK291483 mRNA Translation: BAF84172.1
AK315249 mRNA Translation: BAG37671.1
AC092804 Genomic DNA No translation available.
AC099675 Genomic DNA No translation available.
AL583830 Genomic DNA No translation available.
CH471100 Genomic DNA Translation: EAW93347.1
CH471100 Genomic DNA Translation: EAW93349.1
BC069462 mRNA Translation: AAH69462.1
BC101693 mRNA Translation: AAI01694.1
BC101695 mRNA Translation: AAI01696.1
BC143586 mRNA Translation: AAI43587.1
CCDSiCCDS31024.1 [O95069-2]
CCDS41466.1 [O95069-3]
CCDS41467.1 [O95069-1]
RefSeqiNP_001017424.1, NM_001017424.2 [O95069-3]
NP_001017425.2, NM_001017425.2 [O95069-1]
NP_055032.1, NM_014217.3 [O95069-2]
XP_016856737.1, XM_017001248.1 [O95069-3]
UniGeneiHs.497745

Genome annotation databases

EnsembliENST00000391894; ENSP00000375764; ENSG00000082482 [O95069-2]
ENST00000391895; ENSP00000375765; ENSG00000082482 [O95069-3]
ENST00000444842; ENSP00000394033; ENSG00000082482 [O95069-1]
ENST00000467031; ENSP00000420203; ENSG00000082482 [O95069-4]
GeneIDi3776
KEGGihsa:3776
UCSCiuc001hkq.4 human [O95069-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF129399 mRNA Translation: AAD47569.1
AF171068 mRNA Translation: AAF89743.1
AF004711 mRNA Translation: AAD01203.1
AY552980 mRNA Translation: AAT49015.2
AY552981 mRNA Translation: AAT49016.1
EF165334 mRNA Translation: ABM47413.1
EF165335 mRNA Translation: ABM47414.1
AK291483 mRNA Translation: BAF84172.1
AK315249 mRNA Translation: BAG37671.1
AC092804 Genomic DNA No translation available.
AC099675 Genomic DNA No translation available.
AL583830 Genomic DNA No translation available.
CH471100 Genomic DNA Translation: EAW93347.1
CH471100 Genomic DNA Translation: EAW93349.1
BC069462 mRNA Translation: AAH69462.1
BC101693 mRNA Translation: AAI01694.1
BC101695 mRNA Translation: AAI01696.1
BC143586 mRNA Translation: AAI43587.1
CCDSiCCDS31024.1 [O95069-2]
CCDS41466.1 [O95069-3]
CCDS41467.1 [O95069-1]
RefSeqiNP_001017424.1, NM_001017424.2 [O95069-3]
NP_001017425.2, NM_001017425.2 [O95069-1]
NP_055032.1, NM_014217.3 [O95069-2]
XP_016856737.1, XM_017001248.1 [O95069-3]
UniGeneiHs.497745

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4TWKX-ray2.60A/B41-315[»]
ProteinModelPortaliO95069
SMRiO95069
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9606.ENSP00000394033

Chemistry databases

BindingDBiO95069
ChEMBLiCHEMBL2321615
DrugBankiDB00204 Dofetilide
DB04855 Dronedarone
GuidetoPHARMACOLOGYi514

PTM databases

iPTMnetiO95069
PhosphoSitePlusiO95069

Polymorphism and mutation databases

BioMutaiKCNK2

Proteomic databases

PaxDbiO95069
PeptideAtlasiO95069
PRIDEiO95069
ProteomicsDBi50637
50638 [O95069-2]
50639 [O95069-3]

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000391894; ENSP00000375764; ENSG00000082482 [O95069-2]
ENST00000391895; ENSP00000375765; ENSG00000082482 [O95069-3]
ENST00000444842; ENSP00000394033; ENSG00000082482 [O95069-1]
ENST00000467031; ENSP00000420203; ENSG00000082482 [O95069-4]
GeneIDi3776
KEGGihsa:3776
UCSCiuc001hkq.4 human [O95069-1]

Organism-specific databases

CTDi3776
DisGeNETi3776
EuPathDBiHostDB:ENSG00000082482.13
GeneCardsiKCNK2
HGNCiHGNC:6277 KCNK2
MIMi603219 gene
neXtProtiNX_O95069
OpenTargetsiENSG00000082482
PharmGKBiPA30059
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1418 Eukaryota
COG1226 LUCA
GeneTreeiENSGT00760000118858
HOGENOMiHOG000137657
HOVERGENiHBG055195
InParanoidiO95069
KOiK04913
OMAiTPCKRTL
OrthoDBiEOG091G0E3R
PhylomeDBiO95069
TreeFamiTF313947

Enzyme and pathway databases

ReactomeiR-HSA-1299503 TWIK related potassium channel (TREK)
R-HSA-5576886 Phase 4 - resting membrane potential

Miscellaneous databases

ChiTaRSiKCNK2 human
GeneWikiiKCNK2
GenomeRNAii3776
PROiPR:O95069
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000082482 Expressed in 94 organ(s), highest expression level in left adrenal gland
CleanExiHS_KCNK2
ExpressionAtlasiO95069 baseline and differential
GenevisibleiO95069 HS

Family and domain databases

InterProiView protein in InterPro
IPR003280 2pore_dom_K_chnl
IPR003976 2pore_dom_K_chnl_TREK
IPR013099 K_chnl_dom
PfamiView protein in Pfam
PF07885 Ion_trans_2, 2 hits
PRINTSiPR01333 2POREKCHANEL
PR01499 TREKCHANNEL
ProtoNetiSearch...

Entry informationi

Entry nameiKCNK2_HUMAN
AccessioniPrimary (citable) accession number: O95069
Secondary accession number(s): A1Z1V3
, A8K618, B2RCS4, B7ZL56, D3DTA5, Q5DP47, Q5DP48, Q9NRT2, Q9UNE3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 21, 2001
Last sequence update: April 17, 2007
Last modified: November 7, 2018
This is version 153 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  3. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again