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O95069 (KCNK2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 120. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:KCNK2
Synonyms:TREK, TREK1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length426 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Reversibly converts between a voltage-insensitive potassium leak channel and a voltage-dependent outward rectifying potassium channel in a phosphorylation-dependent manner. Ref.2 Ref.4 Ref.10

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. Ref.2 Ref.4 Ref.10

Subunit structure

Homodimer Potential.

Subcellular location

Isoform 1: Cell membrane; Multi-pass membrane protein By similarity.

Isoform 2: Cell membrane; Multi-pass membrane protein By similarity.

Isoform 4: Endoplasmic reticulum membrane; Multi-pass membrane protein By similarity.

Tissue specificity

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. Ref.4

Domain

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

Post-translational modification

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

Miscellaneous

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

Sequence similarities

Belongs to the two pore domain potassium channel (TC 1.A.1.8) family. [View classification]

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: O95069-1)

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.
Isoform 2 (identifier: O95069-2)

Also known as: TREK-1a;

The sequence of this isoform differs from the canonical sequence as follows:
     2-16: Missing.
Isoform 3 (identifier: O95069-3)

Also known as: TREK-1c;

The sequence of this isoform differs from the canonical sequence as follows:
     1-16: MLPSASRERPGYRAGV → MMNPRAKRDFYL
Isoform 4 (identifier: O95069-4)

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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 426426Potassium channel subfamily K member 2
PRO_0000101742

Regions

Topological domain1 – 6161Cytoplasmic Potential
Transmembrane62 – 8221Helical; Potential
Intramembrane144 – 17027Pore-forming; Name=Pore-forming 1; Potential
Transmembrane172 – 19221Helical; Potential
Topological domain193 – 22331Cytoplasmic Potential
Transmembrane224 – 24421Helical; Potential
Intramembrane253 – 28331Pore-forming; Name=Pore-forming 2; Potential
Transmembrane288 – 30821Helical; Potential
Topological domain309 – 426118Cytoplasmic Potential
Region354 – 42673Required for basal channel activity By similarity
Region378 – 42649Essential for chloroform and halothane sensitivity By similarity

Amino acid modifications

Modified residue3481Phosphoserine; by PKA Ref.10
Glycosylation1101N-linked (GlcNAc...) Potential
Glycosylation1341N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence1 – 1616MLPSA…YRAGV → MMNPRAKRDFYL in isoform 3 and isoform 4.
VSP_024428
Alternative sequence2 – 1615Missing in isoform 2.
VSP_024429
Alternative sequence213 – 23220KWNVS…IFILF → VDPILNIWTSISLSCGSGSL in isoform 4.
VSP_047567
Alternative sequence233 – 426194Missing in isoform 4.
VSP_047568

Experimental info

Mutagenesis3481S → A: Mimics non-phosphorylated state and has no effect on leak channel activity. Ref.10
Mutagenesis3481S → D: Phosphomimetic mutant which causes switch to voltage-dependent outward rectifier channel activity. Ref.10
Sequence conflict309 – 3113DWL → RLV in AAD01203. Ref.3
Sequence conflict3911S → N in AAD47569. Ref.1
Sequence conflict4111T → A in AAD01203. Ref.3

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (TREK-1b) [UniParc].

Last modified April 17, 2007. Version 2.
Checksum: DB10382B1803DA13

FASTA42647,093
        10         20         30         40         50         60 
MLPSASRERP GYRAGVAAPD LLDPKSAAQN SKPRLSFSTK PTVLASRVES DTTINVMKWK 

        70         80         90        100        110        120 
TVSTIFLVVV LYLIIGATVF KALEQPHEIS QRTTIVIQKQ TFISQHSCVN STELDELIQQ 

       130        140        150        160        170        180 
IVAAINAGII PLGNTSNQIS HWDLGSSFFF AGTVITTIGF GNISPRTEGG KIFCIIYALL 

       190        200        210        220        230        240 
GIPLFGFLLA GVGDQLGTIF GKGIAKVEDT FIKWNVSQTK IRIISTIIFI LFGCVLFVAL 

       250        260        270        280        290        300 
PAIIFKHIEG WSALDAIYFV VITLTTIGFG DYVAGGSDIE YLDFYKPVVW FWILVGLAYF 

       310        320        330        340        350        360 
AAVLSMIGDW LRVISKKTKE EVGEFRAHAA EWTANVTAEF KETRRRLSVE IYDKFQRATS 

       370        380        390        400        410        420 
IKRKLSAELA GNHNQELTPC RRTLSVNHLT SERDVLPPLL KTESIYLNGL TPHCAGEEIA 


VIENIK 

« Hide

Isoform 2 (TREK-1a) [UniParc].

Checksum: FDE40CAB21B42A1C
Show »

FASTA41145,495
Isoform 3 (TREK-1c) [UniParc].

Checksum: 1AD4E0B5C1B6CBE7
Show »

FASTA42246,888
Isoform 4 (TREK-1e) [UniParc].

Checksum: 3BEEDE6F7B5EE839
Show »

FASTA22824,682

References

« Hide 'large scale' references
[1]"Inhalational anesthetics activate two-pore-domain background K+ channels."
Patel A.J., Honore E., Lesage F., Fink M., Romey G., Lazdunski M.
Nat. Neurosci. 2:422-426(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), ACTIVATION.
[2]"Cloning, localisation and functional expression of the human orthologue of the TREK-1 potassium channel."
Meadows H.J., Benham C.D., Cairns W., Gloger I., Jennings C., Medhurst A.D., Murdock P., Chapman C.G.
Pflugers Arch. 439:714-722(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION.
Tissue: Brain.
[3]Price L.A., Hellings S.E., Hayashi J.H., Pausch M.H.
Submitted (MAY-1997) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Brain.
[4]"A splice variant of the two-pore domain potassium channel TREK-1 with only one pore domain reduces the surface expression of full-length TREK-1 channels."
Rinne S., Renigunta V., Schlichthorl G., Zuzarte M., Bittner S., Meuth S.G., Decher N., Daut J., Preisig-Muller R.
Pflugers Arch. 0:0-0(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 3 AND 4), FUNCTION, ALTERNATIVE SPLICING, TISSUE SPECIFICITY.
[5]Thomas D., Sullivan A.N., Goldstein S.A.
Submitted (DEC-2006) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Brain and Heart.
[6]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
Tissue: Brain.
[7]"The DNA sequence and biological annotation of human chromosome 1."
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. expand/collapse author list , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Lung.
[10]"KCNK2: reversible conversion of a hippocampal potassium leak into a voltage-dependent channel."
Bockenhauer D., Zilberberg N., Goldstein S.A.
Nat. Neurosci. 4:486-491(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, PHOSPHORYLATION AT SER-348, MUTAGENESIS OF SER-348.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_001017424.1. NM_001017424.2.
NP_001017425.2. NM_001017425.2.
NP_055032.1. NM_014217.3.
UniGeneHs.497745.

3D structure databases

ProteinModelPortalO95069.
SMRO95069. Positions 58-316.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9606.ENSP00000394033.

Chemistry

ChEMBLCHEMBL2321615.
DrugBankDB00204. Dofetilide.
GuidetoPHARMACOLOGY514.

PTM databases

PhosphoSiteO95069.

Proteomic databases

PaxDbO95069.
PRIDEO95069.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000391894; ENSP00000375764; ENSG00000082482. [O95069-2]
ENST00000391895; ENSP00000375765; ENSG00000082482. [O95069-3]
ENST00000444842; ENSP00000394033; ENSG00000082482. [O95069-1]
ENST00000467031; ENSP00000420203; ENSG00000082482. [O95069-4]
GeneID3776.
KEGGhsa:3776.
UCSCuc001hko.3. human. [O95069-3]
uc001hkq.3. human. [O95069-1]
uc001hkr.4. human. [O95069-2]

Organism-specific databases

CTD3776.
GeneCardsGC01P215178.
HGNCHGNC:6277. KCNK2.
HPAHPA056054.
MIM603219. gene.
neXtProtNX_O95069.
PharmGKBPA30059.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1226.
HOVERGENHBG052234.
InParanoidO95069.
KOK04913.
OMAAINVMKW.
PhylomeDBO95069.
TreeFamTF313947.

Enzyme and pathway databases

ReactomeREACT_13685. Neuronal System.

Gene expression databases

ArrayExpressO95069.
BgeeO95069.
CleanExHS_KCNK2.
GenevestigatorO95069.

Family and domain databases

InterProIPR003280. 2pore_dom_K_chnl.
IPR013099. 2pore_dom_K_chnl_dom.
IPR003976. 2pore_dom_K_chnl_TREK.
[Graphical view]
PfamPF07885. Ion_trans_2. 2 hits.
[Graphical view]
PRINTSPR01333. 2POREKCHANEL.
PR01499. TREKCHANNEL.
ProtoNetSearch...

Other

ChiTaRSKCNK2. human.
GeneWikiKCNK2.
GenomeRNAi3776.
NextBio14811.
PROO95069.
SOURCESearch...

Entry information

Entry nameKCNK2_HUMAN
AccessionPrimary (citable) accession number: O95069
Secondary accession number(s): A1Z1V3 expand/collapse secondary AC list , A8K618, B2RCS4, B7ZL56, D3DTA5, Q5DP47, Q5DP48, Q9NRT2, Q9UNE3
Entry history
Integrated into UniProtKB/Swiss-Prot: February 21, 2001
Last sequence update: April 17, 2007
Last modified: April 16, 2014
This is version 120 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM