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Protein

Potassium channel subfamily K member 3

Gene

KCNK3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.1 Publication

GO - Molecular functioni

  1. ion channel activity Source: UniProtKB
  2. open rectifier potassium channel activity Source: Ensembl
  3. potassium channel activity Source: ProtInc
  4. potassium ion leak channel activity Source: UniProtKB
  5. S100 protein binding Source: UniProtKB

GO - Biological processi

  1. brain development Source: Ensembl
  2. cellular response to hypoxia Source: Ensembl
  3. cellular response to zinc ion Source: Ensembl
  4. cochlea development Source: Ensembl
  5. ion transmembrane transport Source: UniProtKB
  6. negative regulation of cytosolic calcium ion concentration Source: Ensembl
  7. potassium ion transport Source: ProtInc
  8. response to drug Source: Ensembl
  9. synaptic transmission Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Ion channel, Potassium channel, Voltage-gated channel

Keywords - Biological processi

Ion transport, Potassium transport, Transport

Keywords - Ligandi

Potassium

Enzyme and pathway databases

ReactomeiREACT_75899. TWIK-releated acid-sensitive K+ channel (TASK).

Protein family/group databases

TCDBi1.A.1.9.2. the voltage-gated ion channel (vic) superfamily.

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:KCNK3
Synonyms:TASK, TASK1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 2

Organism-specific databases

HGNCiHGNC:6278. KCNK3.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 88CytoplasmicSequence Analysis
Transmembranei9 – 2921HelicalSequence AnalysisAdd
BLAST
Intramembranei78 – 10124Pore-forming; Name=Pore-forming 1Sequence AnalysisAdd
BLAST
Transmembranei108 – 12821HelicalSequence AnalysisAdd
BLAST
Topological domaini129 – 15830CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei159 – 17921HelicalSequence AnalysisAdd
BLAST
Intramembranei184 – 20724Pore-forming; Name=Pore-forming 2Sequence AnalysisAdd
BLAST
Transmembranei223 – 24321HelicalSequence AnalysisAdd
BLAST
Topological domaini244 – 394151CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. integral component of plasma membrane Source: ProtInc
  2. plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Involvement in diseasei

Pulmonary hypertension, primary, 4 (PPH4)1 Publication

The disease is caused by mutations affecting the gene represented in this entry.

Disease descriptionA 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.

See also OMIM:615344
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti8 – 81T → K in PPH4; loss of function; channel activity can be rescued with the use of the phospholipase A2 inhibitor ONO-RS-082. 1 Publication
VAR_070126
Natural varianti97 – 971G → R in PPH4; loss of function. 1 Publication
VAR_070127
Natural varianti182 – 1821E → K in PPH4; loss of function; channel activity can be rescued with the use of the phospholipase A2 inhibitor ONO-RS-082. 1 Publication
VAR_070128
Natural varianti192 – 1921Y → C in PPH4; loss of function. 1 Publication
VAR_070129
Natural varianti203 – 2031G → D in PPH4; loss of function; channel activity cannot be rescued with the use of the phospholipase A2 inhibitor ONO-RS-082. 1 Publication
VAR_070130
Natural varianti221 – 2211V → L in PPH4; loss of function. 1 Publication
VAR_070131

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi98 – 981H → N: Greatly reduces pH sensitivity. 1 Publication

Keywords - Diseasei

Disease mutation

Organism-specific databases

MIMi615344. phenotype.
Orphaneti275777. Heritable pulmonary arterial hypertension.
275766. Idiopathic pulmonary arterial hypertension.
PharmGKBiPA30060.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 394394Potassium channel subfamily K member 3PRO_0000101744Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi53 – 531N-linked (GlcNAc...)Sequence Analysis

Keywords - PTMi

Glycoprotein

Proteomic databases

PaxDbiO14649.
PRIDEiO14649.

PTM databases

PhosphoSiteiO14649.

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiO14649.
CleanExiHS_KCNK3.
ExpressionAtlasiO14649. baseline and differential.
GenevestigatoriO14649.

Organism-specific databases

HPAiHPA026658.

Interactioni

Protein-protein interaction databases

BioGridi109978. 3 interactions.
MINTiMINT-1645466.
STRINGi9606.ENSP00000306275.

Structurei

3D structure databases

ProteinModelPortaliO14649.
SMRiO14649. Positions 18-242.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG259548.
GeneTreeiENSGT00760000118858.
HOGENOMiHOG000231463.
HOVERGENiHBG052239.
InParanoidiO14649.
KOiK04914.
OMAiFRSLMKR.
OrthoDBiEOG7B05DC.
PhylomeDBiO14649.
TreeFamiTF313947.

Family and domain databases

InterProiIPR003280. 2pore_dom_K_chnl.
IPR013099. 2pore_dom_K_chnl_dom.
IPR003092. 2pore_dom_K_chnl_TASK.
IPR005406. KCNK3.
[Graphical view]
PfamiPF07885. Ion_trans_2. 2 hits.
[Graphical view]
PIRSFiPIRSF038061. K_channel_subfamily_K_type. 1 hit.
PRINTSiPR01333. 2POREKCHANEL.
PR01584. TASK1CHANNEL.
PR01095. TASKCHANNEL.

Sequencei

Sequence statusi: Complete.

O14649-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MKRQNVRTLA LIVCTFTYLL VGAAVFDALE SEPELIERQR LELRQQELRA
60 70 80 90 100
RYNLSQGGYE ELERVVLRLK PHKAGVQWRF AGSFYFAITV ITTIGYGHAA
110 120 130 140 150
PSTDGGKVFC MFYALLGIPL TLVMFQSLGE RINTLVRYLL HRAKKGLGMR
160 170 180 190 200
RADVSMANMV LIGFFSCIST LCIGAAAFSH YEHWTFFQAY YYCFITLTTI
210 220 230 240 250
GFGDYVALQK DQALQTQPQY VAFSFVYILT GLTVIGAFLN LVVLRFMTMN
260 270 280 290 300
AEDEKRDAEH RALLTRNGQA GGGGGGGSAH TTDTASSTAA AGGGGFRNVY
310 320 330 340 350
AEVLHFQSMC SCLWYKSREK LQYSIPMIIP RDLSTSDTCV EQSHSSPGGG
360 370 380 390
GRYSDTPSRR CLCSGAPRSA ISSVSTGLHS LSTFRGLMKR RSSV
Length:394
Mass (Da):43,518
Last modified:January 1, 1998 - v1
Checksum:i9FF4C8266F615FB7
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti8 – 81T → K in PPH4; loss of function; channel activity can be rescued with the use of the phospholipase A2 inhibitor ONO-RS-082. 1 Publication
VAR_070126
Natural varianti97 – 971G → R in PPH4; loss of function. 1 Publication
VAR_070127
Natural varianti182 – 1821E → K in PPH4; loss of function; channel activity can be rescued with the use of the phospholipase A2 inhibitor ONO-RS-082. 1 Publication
VAR_070128
Natural varianti192 – 1921Y → C in PPH4; loss of function. 1 Publication
VAR_070129
Natural varianti203 – 2031G → D in PPH4; loss of function; channel activity cannot be rescued with the use of the phospholipase A2 inhibitor ONO-RS-082. 1 Publication
VAR_070130
Natural varianti221 – 2211V → L in PPH4; loss of function. 1 Publication
VAR_070131

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS1727.1.
RefSeqiNP_002237.1. NM_002246.2.
UniGeneiHs.645288.

Genome annotation databases

EnsembliENST00000302909; ENSP00000306275; ENSG00000171303.
GeneIDi3777.
KEGGihsa:3777.
UCSCiuc002rhn.2. human.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS1727.1.
RefSeqiNP_002237.1. NM_002246.2.
UniGeneiHs.645288.

3D structure databases

ProteinModelPortaliO14649.
SMRiO14649. Positions 18-242.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109978. 3 interactions.
MINTiMINT-1645466.
STRINGi9606.ENSP00000306275.

Chemistry

BindingDBiO14649.
ChEMBLiCHEMBL2321613.
DrugBankiDB00561. Doxapram.
DB01159. Halothane.
GuidetoPHARMACOLOGYi515.

Protein family/group databases

TCDBi1.A.1.9.2. the voltage-gated ion channel (vic) superfamily.

PTM databases

PhosphoSiteiO14649.

Proteomic databases

PaxDbiO14649.
PRIDEiO14649.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000302909; ENSP00000306275; ENSG00000171303.
GeneIDi3777.
KEGGihsa:3777.
UCSCiuc002rhn.2. human.

Organism-specific databases

CTDi3777.
GeneCardsiGC02P026827.
HGNCiHGNC:6278. KCNK3.
HPAiHPA026658.
MIMi603220. gene.
615344. phenotype.
neXtProtiNX_O14649.
Orphaneti275777. Heritable pulmonary arterial hypertension.
275766. Idiopathic pulmonary arterial hypertension.
PharmGKBiPA30060.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG259548.
GeneTreeiENSGT00760000118858.
HOGENOMiHOG000231463.
HOVERGENiHBG052239.
InParanoidiO14649.
KOiK04914.
OMAiFRSLMKR.
OrthoDBiEOG7B05DC.
PhylomeDBiO14649.
TreeFamiTF313947.

Enzyme and pathway databases

ReactomeiREACT_75899. TWIK-releated acid-sensitive K+ channel (TASK).

Miscellaneous databases

GeneWikiiKCNK3.
GenomeRNAii3777.
NextBioi14819.
PROiO14649.
SOURCEiSearch...

Gene expression databases

BgeeiO14649.
CleanExiHS_KCNK3.
ExpressionAtlasiO14649. baseline and differential.
GenevestigatoriO14649.

Family and domain databases

InterProiIPR003280. 2pore_dom_K_chnl.
IPR013099. 2pore_dom_K_chnl_dom.
IPR003092. 2pore_dom_K_chnl_TASK.
IPR005406. KCNK3.
[Graphical view]
PfamiPF07885. Ion_trans_2. 2 hits.
[Graphical view]
PIRSFiPIRSF038061. K_channel_subfamily_K_type. 1 hit.
PRINTSiPR01333. 2POREKCHANEL.
PR01584. TASK1CHANNEL.
PR01095. TASKCHANNEL.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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(1996) [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(1999) [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.
    , 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(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. 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(1998) [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(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: MUTAGENESIS OF HIS-98.
  7. 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.

Entry informationi

Entry nameiKCNK3_HUMAN
AccessioniPrimary (citable) accession number: O14649
Secondary accession number(s): Q53SU2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 21, 2001
Last sequence update: January 1, 1998
Last modified: January 7, 2015
This is version 128 of the entry and version 1 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

Inhibited by external acidification. Activated by halothane and isoflurane.

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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 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.