Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

O14649 (KCNK3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 122. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Potassium channel subfamily K member 3
Alternative name(s):
Acid-sensitive potassium channel protein TASK-1
TWIK-related acid-sensitive K(+) channel 1
Two pore potassium channel KT3.1
Short name=Two pore K(+) channel KT3.1
Gene names
Name:KCNK3
Synonyms:TASK, TASK1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length394 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

pH-dependent, voltage-insensitive, background potassium channel protein. Rectification direction results from potassium ion concentration on either side of the membrane. Acts as an outward rectifier when external potassium concentration is low. When external potassium concentration is high, current is inward. Ref.1

Subcellular location

Membrane; Multi-pass membrane protein Potential.

Tissue specificity

Widespread expression in adult. Strongest expression in pancreas and placenta. Lower expression in brain, lung, prostate, heart, kidney, uterus, small intestine and colon.

Involvement in disease

Pulmonary hypertension, primary, 4 (PPH4) [MIM:615344]: A rare disorder characterized by plexiform lesions of proliferating endothelial cells in pulmonary arterioles. The lesions lead to elevated pulmonary arterial pression, right ventricular failure, and death. The disease can occur from infancy throughout life and it has a mean age at onset of 36 years. Penetrance is reduced. Although familial pulmonary hypertension is rare, cases secondary to known etiologies are more common and include those associated with the appetite-suppressant drugs.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.7

Miscellaneous

Inhibited by external acidification. Activated by halothane and isoflurane.

Sequence similarities

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

Ontologies

Keywords
   Biological processIon transport
Potassium transport
Transport
   Cellular componentMembrane
   DiseaseDisease mutation
   DomainTransmembrane
Transmembrane helix
   LigandPotassium
   Molecular functionIon channel
Potassium channel
Voltage-gated channel
   PTMGlycoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processbrain development

Inferred from electronic annotation. Source: Ensembl

cellular response to hypoxia

Inferred from electronic annotation. Source: Ensembl

cellular response to zinc ion

Inferred from electronic annotation. Source: Ensembl

cochlea development

Inferred from electronic annotation. Source: Ensembl

ion transmembrane transport

Inferred from mutant phenotype PubMed 12198146. Source: UniProt

negative regulation of cytosolic calcium ion concentration

Inferred from electronic annotation. Source: Ensembl

potassium ion transport

Traceable author statement Ref.1. Source: ProtInc

response to drug

Inferred from electronic annotation. Source: Ensembl

synaptic transmission

Traceable author statement. Source: Reactome

   Cellular_componentintegral component of plasma membrane

Traceable author statement Ref.1. Source: ProtInc

plasma membrane

Inferred from mutant phenotype PubMed 12198146. Source: UniProt

   Molecular_functionS100 protein binding

Inferred from physical interaction PubMed 12198146. Source: UniProt

ion channel activity

Inferred from mutant phenotype PubMed 12198146. Source: UniProt

open rectifier potassium channel activity

Inferred from electronic annotation. Source: Ensembl

potassium channel activity

Traceable author statement Ref.1. Source: ProtInc

potassium ion leak channel activity

Inferred from direct assay Ref.1. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 394394Potassium channel subfamily K member 3
PRO_0000101744

Regions

Topological domain1 – 88Cytoplasmic Potential
Transmembrane9 – 2921Helical; Potential
Intramembrane78 – 10124Pore-forming; Name=Pore-forming 1; Potential
Transmembrane108 – 12821Helical; Potential
Topological domain129 – 15830Cytoplasmic Potential
Transmembrane159 – 17921Helical; Potential
Intramembrane184 – 20724Pore-forming; Name=Pore-forming 2; Potential
Transmembrane223 – 24321Helical; Potential
Topological domain244 – 394151Cytoplasmic Potential

Amino acid modifications

Glycosylation531N-linked (GlcNAc...) Potential

Natural variations

Natural variant81T → K in PPH4; loss of function; channel activity can be rescued with the use of the phospholipase A2 inhibitor ONO-RS-082. Ref.7
VAR_070126
Natural variant971G → R in PPH4; loss of function. Ref.7
VAR_070127
Natural variant1821E → K in PPH4; loss of function; channel activity can be rescued with the use of the phospholipase A2 inhibitor ONO-RS-082. Ref.7
VAR_070128
Natural variant1921Y → C in PPH4; loss of function. Ref.7
VAR_070129
Natural variant2031G → D in PPH4; loss of function; channel activity cannot be rescued with the use of the phospholipase A2 inhibitor ONO-RS-082. Ref.7
VAR_070130
Natural variant2211V → L in PPH4; loss of function. Ref.7
VAR_070131

Experimental info

Mutagenesis981H → N: Greatly reduces pH sensitivity. Ref.6

Sequences

Sequence LengthMass (Da)Tools
O14649 [UniParc].

Last modified January 1, 1998. Version 1.
Checksum: 9FF4C8266F615FB7

FASTA39443,518
        10         20         30         40         50         60 
MKRQNVRTLA LIVCTFTYLL VGAAVFDALE SEPELIERQR LELRQQELRA RYNLSQGGYE 

        70         80         90        100        110        120 
ELERVVLRLK PHKAGVQWRF AGSFYFAITV ITTIGYGHAA PSTDGGKVFC MFYALLGIPL 

       130        140        150        160        170        180 
TLVMFQSLGE RINTLVRYLL HRAKKGLGMR RADVSMANMV LIGFFSCIST LCIGAAAFSH 

       190        200        210        220        230        240 
YEHWTFFQAY YYCFITLTTI GFGDYVALQK DQALQTQPQY VAFSFVYILT GLTVIGAFLN 

       250        260        270        280        290        300 
LVVLRFMTMN AEDEKRDAEH RALLTRNGQA GGGGGGGSAH TTDTASSTAA AGGGGFRNVY 

       310        320        330        340        350        360 
AEVLHFQSMC SCLWYKSREK LQYSIPMIIP RDLSTSDTCV EQSHSSPGGG GRYSDTPSRR 

       370        380        390 
CLCSGAPRSA ISSVSTGLHS LSTFRGLMKR RSSV 

« Hide

References

« Hide 'large scale' references
[1]"TASK, a human background K+ channel to sense external pH variations near physiological pH."
Duprat F., Lesage F., Fink M., Reyes R., Heurteaux C., Lazdunski M.
EMBO J. 16:5464-5471(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION.
Tissue: Kidney.
[2]"Proton block and voltage gating are potassium-dependent in the cardiac leak channel Kcnk3."
Lopes C.M.B., Gallagher P.G., Buck M.E., Butler M.H., Goldstein S.A.N.
J. Biol. Chem. 275:16969-16978(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Heart.
[3]"Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. expand/collapse author list , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]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].
[5]"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: ACTIVATION.
[6]"TASK-5, a novel member of the tandem pore K+ channel family."
Ashmole I., Goodwin P.A., Stanfield P.R.
Pflugers Arch. 442:828-833(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF HIS-98.
[7]"A novel channelopathy in pulmonary arterial hypertension."
Ma L., Roman-Campos D., Austin E.D., Eyries M., Sampson K.S., Soubrier F., Germain M., Tregouet D.A., Borczuk A., Rosenzweig E.B., Girerd B., Montani D., Humbert M., Loyd J.E., Kass R.S., Chung W.K.
N. Engl. J. Med. 369:351-361(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PPH4 LYS-8; ARG-97; LYS-182; CYS-192; ASP-203 AND LEU-221, CHARACTERIZATION OF VARIANTS PPH4 LYS-8; ARG-97; LYS-182; CYS-192; ASP-203 AND LEU-221.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF006823 mRNA. Translation: AAC51777.1.
AF065163 mRNA. Translation: AAG29340.1.
AC015977 Genomic DNA. Translation: AAY24312.1.
CH471053 Genomic DNA. Translation: EAX00678.1.
CH471053 Genomic DNA. Translation: EAX00679.1.
RefSeqNP_002237.1. NM_002246.2.
UniGeneHs.645288.

3D structure databases

ProteinModelPortalO14649.
SMRO14649. Positions 18-242.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109978. 3 interactions.
MINTMINT-1645466.
STRING9606.ENSP00000306275.

Chemistry

ChEMBLCHEMBL2321613.
GuidetoPHARMACOLOGY515.

Protein family/group databases

TCDB1.A.1.9.2. the voltage-gated ion channel (vic) superfamily.

PTM databases

PhosphoSiteO14649.

Proteomic databases

PaxDbO14649.
PRIDEO14649.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000302909; ENSP00000306275; ENSG00000171303.
GeneID3777.
KEGGhsa:3777.
UCSCuc002rhn.2. human.

Organism-specific databases

CTD3777.
GeneCardsGC02P026827.
HGNCHGNC:6278. KCNK3.
HPAHPA026658.
MIM603220. gene.
615344. phenotype.
neXtProtNX_O14649.
Orphanet275777. Heritable pulmonary arterial hypertension.
275766. Idiopathic pulmonary arterial hypertension.
PharmGKBPA30060.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG259548.
HOGENOMHOG000231463.
HOVERGENHBG052239.
InParanoidO14649.
KOK04914.
OMACSGTQRS.
OrthoDBEOG7B05DC.
PhylomeDBO14649.
TreeFamTF313947.

Enzyme and pathway databases

ReactomeREACT_13685. Neuronal System.

Gene expression databases

ArrayExpressO14649.
BgeeO14649.
CleanExHS_KCNK3.
GenevestigatorO14649.

Family and domain databases

InterProIPR003280. 2pore_dom_K_chnl.
IPR013099. 2pore_dom_K_chnl_dom.
IPR003092. 2pore_dom_K_chnl_TASK.
IPR005406. KCNK3.
[Graphical view]
PfamPF07885. Ion_trans_2. 2 hits.
[Graphical view]
PIRSFPIRSF038061. K_channel_subfamily_K_type. 1 hit.
PRINTSPR01333. 2POREKCHANEL.
PR01584. TASK1CHANNEL.
PR01095. TASKCHANNEL.
ProtoNetSearch...

Other

GeneWikiKCNK3.
GenomeRNAi3777.
NextBio14819.
PROO14649.
SOURCESearch...

Entry information

Entry nameKCNK3_HUMAN
AccessionPrimary (citable) accession number: O14649
Secondary accession number(s): Q53SU2
Entry history
Integrated into UniProtKB/Swiss-Prot: February 21, 2001
Last sequence update: January 1, 1998
Last modified: April 16, 2014
This is version 122 of the entry and version 1 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 polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 2

Human chromosome 2: entries, gene names and cross-references to MIM