Kcnk18

Functionⁱ

Outward rectifying potassium channel. Produces rapidly activating outward rectifier K⁺ currents. May function as background potassium channel that sets the resting membrane potential. Channel activity is directly activated by calcium signal. Activated by the G(q)-protein coupled receptor pathway. The calcium signal robustly activates the channel via calcineurin, whereas the anchoring of 14-3-3/YWHAH interferes with the return of the current to the resting state after activation. Inhibited also by arachidonic acid and other naturally occurring unsaturated free fatty acids. Channel activity is also enhanced by volatile anesthetics, such as isoflurane. Appears to be the primary target of hydroxy-alpha-sanshool, an ingredient of Schezuan pepper. May be involved in the somatosensory function with special respect to pain sensation.3 Publications

Miscellaneous

Regulated by extracellular protons whereas human ortholog is not. His-132 is responsible for proton-dependent specific activity.

GO - Molecular functionⁱ

calcium-activated potassium channel activity
Source: UniProtKB
Inferred from direct assayⁱ
- 20006580
outward rectifier potassium channel activity Source: MGI
potassium ion leak channel activity Source: GO_Central

Complete GO annotation...

GO - Biological processⁱ

cellular response to pH Source: MGI
potassium ion export Source: MGI
potassium ion transport
Source: UniProtKB
Inferred from direct assayⁱ
- 20006580
stabilization of membrane potential Source: GO_Central

Complete GO annotation...

Keywordsⁱ

Molecular function	Ion channel, Potassium channel
Biological process	Ion transport, Potassium transport, Transport
Ligand	Potassium

Enzyme and pathway databases

Reactomeⁱ	R-MMU-1299344. TWIK-related spinal cord K+ channel (TRESK).

Reactomeⁱ

R-MMU-1299344. TWIK-related spinal cord K+ channel (TRESK).

Protein family/group databases

TCDBⁱ	1.A.1.18.1. the voltage-gated ion channel (vic) superfamily.

TCDBⁱ

1.A.1.18.1. the voltage-gated ion channel (vic) superfamily.

Names & Taxonomyⁱ

Protein namesⁱ	Recommended name: Potassium channel subfamily K member 18 Alternative name(s): Two-pore-domain potassium channel TRESK
Gene namesⁱ	Name:Kcnk18 Synonyms:Tresk-2, Tresk2
Organismⁱ	Mus musculus (Mouse)
Taxonomic identifierⁱ	10090 [NCBI]
Taxonomic lineageⁱ	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus
Proteomesⁱ	UP000000589 Componentⁱ: Chromosome 19

Organism-specific databases

MGIⁱ	MGI:2685627. Kcnk18.

Subcellular locationⁱ

Cell membrane
1 Publication
Manual assertion based on experiment inⁱ
- Ref.9
  "N-linked glycosylation determines cell surface expression of two-pore-domain K+ channel TRESK."
  Egenberger B., Polleichtner G., Wischmeyer E., Doring F.
  Biochem. Biophys. Res. Commun. 391:1262-1267(2010) [PubMed] [Europe PMC] [Abstract]
  Cited for: SUBCELLULAR LOCATION, GLYCOSYLATION AT ASN-83, MUTAGENESIS OF ASN-83.
; Multi-pass membrane protein
1 Publication
Manual assertion based on experiment inⁱ
- Ref.9
  "N-linked glycosylation determines cell surface expression of two-pore-domain K+ channel TRESK."
  Egenberger B., Polleichtner G., Wischmeyer E., Doring F.
  Biochem. Biophys. Res. Commun. 391:1262-1267(2010) [PubMed] [Europe PMC] [Abstract]
  Cited for: SUBCELLULAR LOCATION, GLYCOSYLATION AT ASN-83, MUTAGENESIS OF ASN-83.

Topology

Feature key	Position(s)	DescriptionActions	Length
Topological domainⁱ	1 – 31	CytoplasmicSequence analysisAdd BLAST	31
Transmembraneⁱ	32 – 52	HelicalSequence analysisAdd BLAST	21
Intramembraneⁱ	114 – 140	Pore-forming; Name=Pore-forming 1Sequence analysisAdd BLAST	27
Transmembraneⁱ	142 – 162	HelicalSequence analysisAdd BLAST	21
Topological domainⁱ	163 – 292	CytoplasmicSequence analysisAdd BLAST	130
Transmembraneⁱ	293 – 313	HelicalSequence analysisAdd BLAST	21
Intramembraneⁱ	326 – 340	Pore-forming; Name=Pore-forming 2Sequence analysisAdd BLAST	15
Transmembraneⁱ	347 – 367	HelicalSequence analysisAdd BLAST	21
Topological domainⁱ	368 – 394	CytoplasmicSequence analysisAdd BLAST	27

GO - Cellular componentⁱ

integral component of plasma membrane Source: GO_Central
plasma membrane
Source: UniProtKB
Inferred from direct assayⁱ
- 20006580

Complete GO annotation...

Keywords - Cellular componentⁱ

Cell membrane, Membrane

Pathology & Biotechⁱ

Mutagenesis

Feature key	Position(s)	DescriptionActions	Length
Mutagenesisⁱ	83	N → Q: Strongly reduced current amplitude and localization to cell membrane. 1 Publication	1
Mutagenesisⁱ	132	H → N: Insensitive to extracellular protons. 1 Publication	1
Mutagenesisⁱ	212	I → A: Loss of interaction with calcineurin and activation by elevated intracellular calcium; when associated with A-214.	1
Mutagenesisⁱ	214	I → A: Strongly reduced activation by elevated intracellular calcium. Loss of interaction with calcineurin and activation by elevated intracellular calcium; when associated with A-212.	1
Mutagenesisⁱ	264	S → A: Loss of interaction with YWHAH. 1 Publication	1
Mutagenesisⁱ	276	S → A: Enhances basal channel activity and abolishes stimulation by calcineurin. 1 Publication	1

PTM / Processingⁱ

Molecule processing

Feature key	Position(s)	DescriptionActions	Graphical view	Length
ChainⁱPRO_0000312501	1 – 394	Potassium channel subfamily K member 18Add BLAST		394

Amino acid modifications

Feature key	Position(s)	DescriptionActions	Length
Glycosylationⁱ	83	N-linked (GlcNAc...) asparagine1 Publication	1
Modified residueⁱ	264	Phosphoserine1 Publication	1
Modified residueⁱ	276	Phosphoserine1 Publication	1

Post-translational modificationⁱ

Phosphorylation of Ser-264 is required for the binding of 14-3-3eta/YWHAH. Calcineurin-mediated dephosphorylation of Ser-276 enhances channel activity.2 Publications

N-glycosylated.1 Publication

Keywords - PTMⁱ

Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbⁱ	Q6VV64.
PRIDEⁱ	Q6VV64.

PTM databases

iPTMnetⁱ	Q6VV64.
PhosphoSitePlusⁱ	Q6VV64.

Expressionⁱ

Tissue specificityⁱ

Detected in brain cortex, cerebellum, dorsal root ganglion, spinal cord and testis. High expression in trigeminal ganglion, also expressed in autonomic nervous system ganglia such as the stellate ganglion and paravertebral sympathetic ganglia. Expressed in all adult spinal cord and brain regions, with slightly higher expression in thalamus, hypothalamus, hippocampus and posterior corte (at protein level). In non-neuronal tissues, substantial expression found in lung and heart and weal expression in liver, testis, kidney, small intestine and spleen.4 Publications

Developmental stageⁱ

Expression appears in trigeminal ganglion and dorsal root ganglia from E15.5 and increased through E18 to reach a peak in newborn mouse postnatal day 1.1 Publication

Gene expression databases

Bgeeⁱ	ENSMUSG00000040901.
CleanExⁱ	MM_KCNK18.

Interactionⁱ

Subunit structureⁱ

Interacts with calcineurin. Interacts with YWHAH, in a phosphorylation-dependent manner.2 Publications

Protein-protein interaction databases

IntActⁱ	Q6VV64. 1 interactor.
Molecular INTeraction database More...MINTⁱ	MINT-7997383.
STRINGⁱ	10090.ENSMUSP00000065713.

Structureⁱ

3D structure databases

ProteinModelPortalⁱ	Q6VV64.
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Family & Domainsⁱ

Region

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Regionⁱ	210 – 215	Interaction with calcineurin		6
Regionⁱ	261 – 266	Interaction with YWHAH1 Publication		6

Sequence similaritiesⁱ

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

Keywords - Domainⁱ

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGⁱ	KOG1418. Eukaryota. COG1226. LUCA.
Ensembl GeneTree More...GeneTreeⁱ	ENSGT00700000104522.
HOGENOMⁱ	HOG000074045.
HOVERGENⁱ	HBG104673.
InParanoidⁱ	Q6VV64.
KEGG Orthology (KO) More...KOⁱ	K20007.
OMAⁱ	FKLVQNR.
Database of Orthologous Groups More...OrthoDBⁱ	EOG091G0B4G.
PhylomeDBⁱ	Q6VV64.
TreeFamⁱ	TF316115.

Family and domain databases

InterProⁱ	View protein in InterPro IPR003280. 2pore_dom_K_chnl. IPR003092. 2pore_dom_K_chnl_TASK. IPR013099. K_chnl_dom.
Pfam protein domain database More...Pfamⁱ	View protein in Pfam PF07885. Ion_trans_2. 2 hits.
PRINTSⁱ	PR01333. 2POREKCHANEL. PR01095. TASKCHANNEL.

Sequenceⁱ

Sequence statusⁱ: Complete.

Q6VV64-1 [UniParc]FASTA Add to basket

« Hide

        10         20         30         40         50
MEAEEPPEAR RCCPEALGKA RGCCPEALGK LLPGLCFLCC LVTYALVGAA 
        60         70         80         90        100
LFSAVEGRPD PEAEENPELK KFLDDLCNIL KCNLTVVEGS RKNLCEHLQH 
       110        120        130        140        150
LKPQWLKAPQ DWSFLSALFF CCTVFSTVGY GHMYPVTRLG KFLCMLYALF 
       160        170        180        190        200
GIPLMFLVLT DIGDILATIL SRAYSRFQAL LCLPHDIFKW RSLPLCRKQP 
       210        220        230        240        250
DSKPVEEAIP QIVIDAGVDE LLNPQPSKDP PSPSCNVELF ERLVAREKKN 
       260        270        280        290        300
KLQPPTRPVE RSNSCPELVL GRLSCSILSN LDEVGQQVER LDIPLPVIAL 
       310        320        330        340        350
VVFAYISCAA AILPFWETEL GFEDAFYFCF VTLTTIGFGD IVLVHPHFFL 
       360        370        380        390 
FFSIYIIVGM EILFIAFKLM QNRLLHTYKT LMLFVCQREV SLPW

Length:394

Mass (Da):44,403

Last modified:July 5, 2004 - v1

Checksum:ⁱ82D03F7D7F0D5591

GO

Experimental Info

Feature key	Position(s)	DescriptionActions	Length
Sequence conflictⁱ	228	K → R in AAI15706 (PubMed:15489334).Curated	1
Sequence conflictⁱ	228	K → R in AAI04133 (PubMed:15489334).Curated	1
Sequence conflictⁱ	251	K → E in AAI15706 (PubMed:15489334).Curated	1
Sequence conflictⁱ	251	K → E in AAI04133 (PubMed:15489334).Curated	1

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	AY325301 mRNA. Translation: AAQ91836.1. AY542902 mRNA. Translation: AAS48426.1. AK139600 mRNA. Translation: BAE24080.1. AK162136 mRNA. Translation: BAE36746.1. BC104132 mRNA. Translation: AAI04133.1. BC104133 mRNA. Translation: AAI04134.1. BC115705 mRNA. Translation: AAI15706.1. BC115887 mRNA. Translation: AAI15888.1. BC127136 mRNA. Translation: AAI27137.1. BC127137 mRNA. Translation: AAI27138.1.
The Consensus CDS (CCDS) project More...CCDSⁱ	CCDS29934.1.
NCBI Reference Sequences More...RefSeqⁱ	NP_997144.1. NM_207261.3.
UniGeneⁱ	Mm.329947.

Genome annotation databases

Ensemblⁱ	ENSMUST00000065204; ENSMUSP00000065713; ENSMUSG00000040901.
GeneIDⁱ	332396.
KEGGⁱ	mmu:332396.
UCSC genome browser More...UCSCⁱ	uc008ibh.1. mouse.

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.

Cross-referencesⁱ

Web resourcesⁱ

Protein Spotlight

Throb - Issue 124 of December 2010

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	AY325301 mRNA. Translation: AAQ91836.1. AY542902 mRNA. Translation: AAS48426.1. AK139600 mRNA. Translation: BAE24080.1. AK162136 mRNA. Translation: BAE36746.1. BC104132 mRNA. Translation: AAI04133.1. BC104133 mRNA. Translation: AAI04134.1. BC115705 mRNA. Translation: AAI15706.1. BC115887 mRNA. Translation: AAI15888.1. BC127136 mRNA. Translation: AAI27137.1. BC127137 mRNA. Translation: AAI27138.1.
The Consensus CDS (CCDS) project More...CCDSⁱ	CCDS29934.1.
NCBI Reference Sequences More...RefSeqⁱ	NP_997144.1. NM_207261.3.
UniGeneⁱ	Mm.329947.

3D structure databases

ProteinModelPortalⁱ	Q6VV64.
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Protein-protein interaction databases

IntActⁱ	Q6VV64. 1 interactor.
Molecular INTeraction database More...MINTⁱ	MINT-7997383.
STRINGⁱ	10090.ENSMUSP00000065713.

Protein family/group databases

TCDBⁱ	1.A.1.18.1. the voltage-gated ion channel (vic) superfamily.

TCDBⁱ

1.A.1.18.1. the voltage-gated ion channel (vic) superfamily.

PTM databases

iPTMnetⁱ	Q6VV64.
PhosphoSitePlusⁱ	Q6VV64.

Proteomic databases

PaxDbⁱ	Q6VV64.
PRIDEⁱ	Q6VV64.

Protocols and materials databases

Structural Biology Knowledgebase	Search...

Structural Biology Knowledgebase

Search...

Genome annotation databases

Ensemblⁱ	ENSMUST00000065204; ENSMUSP00000065713; ENSMUSG00000040901.
GeneIDⁱ	332396.
KEGGⁱ	mmu:332396.
UCSC genome browser More...UCSCⁱ	uc008ibh.1. mouse.

Organism-specific databases

CTDⁱ	338567.
MGIⁱ	MGI:2685627. Kcnk18.

Phylogenomic databases

eggNOGⁱ	KOG1418. Eukaryota. COG1226. LUCA.
Ensembl GeneTree More...GeneTreeⁱ	ENSGT00700000104522.
HOGENOMⁱ	HOG000074045.
HOVERGENⁱ	HBG104673.
InParanoidⁱ	Q6VV64.
KEGG Orthology (KO) More...KOⁱ	K20007.
OMAⁱ	FKLVQNR.
Database of Orthologous Groups More...OrthoDBⁱ	EOG091G0B4G.
PhylomeDBⁱ	Q6VV64.
TreeFamⁱ	TF316115.

Enzyme and pathway databases

Reactomeⁱ	R-MMU-1299344. TWIK-related spinal cord K+ channel (TRESK).

Reactomeⁱ

R-MMU-1299344. TWIK-related spinal cord K+ channel (TRESK).

Miscellaneous databases

Protein Ontology More...PROⁱ	PR:Q6VV64.
SOURCEⁱ	Search...

Gene expression databases

Bgeeⁱ	ENSMUSG00000040901.
CleanExⁱ	MM_KCNK18.

Family and domain databases

InterProⁱ	View protein in InterPro IPR003280. 2pore_dom_K_chnl. IPR003092. 2pore_dom_K_chnl_TASK. IPR013099. K_chnl_dom.
Pfam protein domain database More...Pfamⁱ	View protein in Pfam PF07885. Ion_trans_2. 2 hits.
PRINTSⁱ	PR01333. 2POREKCHANEL. PR01095. TASKCHANNEL.
ProtoNetⁱ	Search...

Entry informationⁱ

Entry nameⁱ	KCNKI_MOUSE
Accessionⁱ	Q6VV64Primary (citable) accession number: Q6VV64 Secondary accession number(s): Q1LZJ5 , Q1LZM8, Q3MI50, Q3MI51
Entry historyⁱ	Integrated into UniProtKB/Swiss-Prot:	December 4, 2007
	Last sequence update:	July 5, 2004
	Last modified:	July 5, 2017
	This is version 115 of the entry and version 1 of the sequence. See complete history.
Entry statusⁱ	Reviewed (UniProtKB/Swiss-Prot)
Annotation program	Chordata Protein Annotation Program

Miscellaneousⁱ

Keywords - Technical termⁱ

Complete proteome, Reference proteome

Documents

MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
Protein Spotlight
Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries
SIMILARITY comments
Index of protein domains and families

UniProtKB

UniParc

Help

UniRef

Proteomes

Annotation systems

Supporting data

UniProtKB - Q6VV64 (KCNKI_MOUSE)

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Potassium channel subfamily K member 18

Select a section on the left to see content.

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

Miscellaneous

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Biological processi

Enzyme and pathway databases

Protein family/group databases

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

Organism-specific databases

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Topology

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Cellular componenti

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

Mutagenesis

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Amino acid modifications

Proteomic databases

PTM databases

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

Gene expression databases

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

Protein-protein interaction databases

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

3D structure databases

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Region

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Phylogenomic databases

Family and domain databases

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including length and molecular weight.<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequencei

Experimental Info

Sequence databases

Genome annotation databases

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

<p>This subsection of the <a href="http://www.uniprot.org/manual/cross_references_section">Cross-references</a> section provides links to various web resources that are relevant for a specific protein.<p><a href='/help/web_resource' target='_top'>More...</a></p>Web resourcesi

Sequence databases

3D structure databases

Protein-protein interaction databases

Protein family/group databases

PTM databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Miscellaneous databases

Gene expression databases

Family and domain databases

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Documents

Functionⁱ

GO - Molecular functionⁱ

GO - Biological processⁱ

Names & Taxonomyⁱ

Subcellular locationⁱ

GO - Cellular componentⁱ

Pathology & Biotechⁱ

PTM / Processingⁱ

Expressionⁱ

Interactionⁱ

Structureⁱ

Family & Domainsⁱ

Sequence similaritiesⁱ

Sequenceⁱ

Cross-referencesⁱ

Web resourcesⁱ

Entry informationⁱ

Miscellaneousⁱ