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Protein

Potassium channel subfamily K member 2

Gene

KCNK2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Ion channel, Potassium channel

Keywords - Biological processi

Ion transport, Potassium transport, Transport

Keywords - Ligandi

Potassium

Enzyme and pathway databases

BioCyciZFISH:ENSG00000082482-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 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

HGNCiHGNC:6277. KCNK2.

Subcellular locationi

Isoform 1 :
Isoform 2 :

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

GO - Cellular componenti

Complete GO annotation...

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...)Sequence analysisCombined sources1
Glycosylationi134N-linked (GlcNAc...)Sequence 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.

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.
CleanExiHS_KCNK2.
ExpressionAtlasiO95069. baseline and differential.
GenevisibleiO95069. HS.

Organism-specific databases

HPAiHPA056054.

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
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi54 – 105Combined sources52
Helixi111 – 127Combined sources17
Turni133 – 137Combined sources5
Beta strandi141 – 143Combined sources3
Helixi144 – 155Combined sources12
Helixi168 – 213Combined sources46
Helixi218 – 237Combined sources20
Helixi242 – 247Combined sources6
Helixi253 – 264Combined sources12
Helixi287 – 315Combined sources29

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...

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.
HOVERGENiHBG052234.
InParanoidiO95069.
KOiK04913.
OMAiAINVMKW.
OrthoDBiEOG091G0E3R.
PhylomeDBiO95069.
TreeFamiTF313947.

Family and domain databases

InterProiIPR003280. 2pore_dom_K_chnl.
IPR003976. 2pore_dom_K_chnl_TREK.
IPR013099. K_chnl_dom.
[Graphical view]
PfamiPF07885. Ion_trans_2. 2 hits.
[Graphical view]
PRINTSiPR01333. 2POREKCHANEL.
PR01499. TREKCHANNEL.

Sequences (4)i

Sequence statusi: Complete.

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

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

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

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.

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.
GeneCardsiKCNK2.
HGNCiHGNC:6277. KCNK2.
HPAiHPA056054.
MIMi603219. gene.
neXtProtiNX_O95069.
OpenTargetsiENSG00000082482.
PharmGKBiPA30059.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1418. Eukaryota.
COG1226. LUCA.
GeneTreeiENSGT00760000118858.
HOGENOMiHOG000137657.
HOVERGENiHBG052234.
InParanoidiO95069.
KOiK04913.
OMAiAINVMKW.
OrthoDBiEOG091G0E3R.
PhylomeDBiO95069.
TreeFamiTF313947.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000082482-MONOMER.
ReactomeiR-HSA-1299503. TWIK related potassium channel (TREK).
R-HSA-5576886. Phase 4 - resting membrane potential.

Miscellaneous databases

ChiTaRSiKCNK2. human.
GeneWikiiKCNK2.
GenomeRNAii3776.
PROiO95069.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000082482.
CleanExiHS_KCNK2.
ExpressionAtlasiO95069. baseline and differential.
GenevisibleiO95069. HS.

Family and domain databases

InterProiIPR003280. 2pore_dom_K_chnl.
IPR003976. 2pore_dom_K_chnl_TREK.
IPR013099. K_chnl_dom.
[Graphical view]
PfamiPF07885. Ion_trans_2. 2 hits.
[Graphical view]
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 historyi
Integrated into UniProtKB/Swiss-Prot: February 21, 2001
Last sequence update: April 17, 2007
Last modified: November 2, 2016
This is version 143 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

Miscellaneous

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

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. 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.